Low-dose aspirin for the prevention of preterm birth in nulliparous women: systematic review and meta-analysis.

OBJECTIVE: The objective was to assess the efficacy and safety of low-dose aspirin for the prevention of preterm birth in nulliparous women. DATA SOURCES: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to June 2022. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared aspirin to placebo in nulliparous women were eligible. METHODS: This study was reported in accordance with the PRISMA 2020 checklist. The primary outcomes of this study were the rates of preterm birth at less than 37 weeks and less than 34 weeks of gestation. The secondary outcomes included postpartum hemorrhage, placental abruption, cesarean section, any hypertensive disorder of pregnancy and small for gestational age. Relative risks with their 95% confidence intervals were calculated for analysis. Heterogeneity was assessed by Cochran's Q test and Higgins's I2. A random-effects model was used when I2 was > 50% to generate the RR and 95% CI; otherwise, a fixed-effects model was used. The risk of publication bias was assessed by funnel plots. We performed sensitivity analysis by sequentially omitting each included study to confirm the robustness of the analysis. RESULTS: Seven studies with a total of 29,029 participants were included in this review. Six studies were assessed as having a low risk of bias or an unclear risk of bias, and one study was judged as having a high risk of bias. In nulliparous women, low-dose aspirin was associated with a significant reduction in the rate of preterm birth at less than 34 weeks of gestational age (RR 0.84,95% CI: 0.71-0.99; I2 = 0%; P = 0.04), but we did not observe a significant difference in the rate of preterm birth at less than 37 weeks of gestation (RR 0.96,95% CI: 0.90-1.02; I2 = 31%; P = 0.18). Low-dose aspirin was associated with a significant increase in the rates of postpartum hemorrhage (RR 1.32,95% CI: 1.14-1.54; I2 = 0%; P = 0.0003), placental abruption (RR 2.18,95% CI: 1.10-4.32; I2 = 16%; P = 0.02) and cesarean section (RR 1.053, 95% CI: 1.001-1.108; I2 = 0%; P = 0.05) in nulliparous women. We also did not observe a significant effect of low-dose aspirin on the rates of any hypertensive disorder of pregnancy (RR 1.05, 95% CI: 0.96-1.14; I2 = 9%; P = 0.28) or small for gestational age (RR 0.96, 95% CI: 0.91-1.02; I2 = 0%; P = 0.16) in nulliparous women. Funnel plots indicated that no significant publication bias existed in this meta-analysis. Except for preterm birth at less than 34 weeks of gestation, placental abruption and cesarean section, the sensitivity analysis showed similar results, which confirmed the robustness of this meta-analysis. CONCLUSIONS: Low-dose aspirin might reduce the risk of preterm birth at less than 34 weeks of gestation in nulliparous women. The use of low-dose aspirin in nulliparous women increased the risk of postpartum hemorrhage and might increase the risk of placental abruption and cesarean section.

Potential prevention of stillbirth caused by placental abruption: a regional population-based study in Japan.

OBJECTIVE: Placental abruption is associated with adverse perinatal outcomes including intrauterine fetal demise, which subsequently results in stillbirth. However, few studies have demonstrated the preventability of stillbirth due to placental abruption. Therefore, we evaluated the possibility of preventing stillbirth caused by placental abruption by reviewing all stillbirths in our region. METHODS: This study reviewed all stillbirths after 22 weeks of gestation in Shiga Prefecture, Japan from 2010 to 2019, excluding lethal disorders. We evaluated 350 stillbirth cases, with and without placental abruption. RESULTS: There were 32 stillbirths with PA and 318 without placental abruption. The probability of preventing stillbirth was significantly higher in patients with placental abruption than in those without (30% vs. 8%, p < 0.001). We also determined the recommendations for preventing stillbirths with placental abruption. CONCLUSION: Some stillbirths caused by placental abruption can be prevented. We recommend improvements to perinatal maternal-fetal care and perinatal emergency transport systems.

Maternal-neonatal events resulting from medications for preventing hypertensive disorders in high-risk pregnant women: A systematic review and network meta-analysis.

BACKGROUND: There have been few studies reporting on maternal and neonatal events in high-risk pregnant women receiving medications for preventing hypertensive disorders of pregnancy (HDP). OBJECTIVE: To identify placental abruption, postpartum hemorrhage, neonatal intraventricular hemorrhage, and neonates with small for gestational age (SGA) or growth restriction resulting from medications for preventing HDP in high-risk pregnant women using a network meta-analysis. SEARCH STRATEGY: All randomized controlled trials comparing the most commonly used medications (antiplatelet agents, anticoagulants, antioxidants, nitric oxide, and calcium) for preventing HDP in high-risk pregnant women were searched from the Cochrane Pregnancy and Childbirth's Specialized Register of Controlled Trials until July 31, 2020, without language restriction. SELECTION CRITERIA: Two of the authors independently selected the eligible trials. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and assessed the methodological quality of the included trials. Pairwise and network meta-analyses were used to determine comparative risk ratios and 95% confidence intervals. MAIN RESULTS: The 51 included trials involved 69 669 pregnant women. Compared with placebo/no treatment, antioxidants slightly reduced placental abruption with high-certainty evidence. Antiplatelet agents probably reduced SGA with low-certainty evidence and slightly increased neonatal intraventricular hemorrhage with moderate-certainty evidence. CONCLUSION: Antiplatelet agents probably reduce SGA, but neonatal intraventricular hemorrhage should be monitored. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018096276.

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

ACOG Practice Bulletin No. 188: Prelabor Rupture of Membranes.

Preterm delivery occurs in approximately 12% of all births in the United States and is a major factor that contributes to perinatal morbidity and mortality (1, 2). Preterm prelabor rupture of membranes (also referred to as premature rupture of membranes) (PROM) complicates approximately 3% of all pregnancies in the United States (3). The optimal approach to clinical assessment and treatment of women with term and preterm PROM remains controversial. Management hinges on knowledge of gestational age and evaluation of the relative risks of delivery versus the risks of expectant management (eg, infection, abruptio placentae, and umbilical cord accident). The purpose of this document is to review the current understanding of this condition and to provide management guidelines that have been validated by appropriately conducted outcome-based research when available. Additional guidelines on the basis of consensus and expert opinion also are presented.

Cesación de tabaquismo en embarazo / Smoking cessation in pregnancy

Resumen En Chile, las mujeres en edad fértil y las embarazadas presentan una alta prevalencia de tabaquismo. El consumo de tabaco durante el embarazo tiene efectos prenatales (por ejemplo, aborto espontáneo, mortinatalidad) y es un factor de riesgo de morbilidad y mortalidad infantil. Todas las mujeres en edad fértil deben ser alentadas a dejar de fumar, y las mujeres que ya están embarazadas deben ser alentadas a dejar de fumar continuamente durante todo el embarazo, desde el momento más precoz posible hasta el período posterior al parto. Se presenta un conjunto de antecedentes y recomendaciones para la cesación de tabaquismo en embarazadas, basadas en guías internacionales sobre este tema.

In Chile, women of childbearing age and pregnant women have a high prevalence of smoking. Tobacco use during pregnancy has antenatal effects (spontaneous abortion, stillbirth) and it is a risk factor for infant morbidity and mortality. All women of childbearing age should be encouraged to quit smoking, and women who are already pregnant should be encouraged to stop smoking continuously throughout the pregnancy, from the earliest possible moment to the postpartum period. We present a set of background information and recommendations for smoking cessation in pregnant women, based on international guidelines on this topic.

An update on the risk factors for and management of obstetric haemorrhage.

Obstetric haemorrhage is associated with increased risk of serious maternal morbidity and mortality. Postpartum haemorrhage is the commonest form of obstetric haemorrhage, and worldwide, a woman dies due to massive postpartum haemorrhage approximately every 4 min. In addition, many experience serious morbidity such as multi-organ failure, complications of multiple blood transfusions, peripartum hysterectomy and unintended damage to pelvic organs, loss of fertility and psychological sequelae, including posttraumatic stress disorders. Anticipation of massive postpartum haemorrhage, prompt recognition of the cause and institution of timely and appropriate measures to control bleeding and replacement of the lost blood volume and restoration of oxygen carrying capacity (i.e. haemoglobin) and correction of the 'washout phenomenon' leading to coagulopathy will help save lives. Obstetric shock index may help in avoidance of underestimation of blood loss and the use of tranexamic acid, oxytocics and timely peripartum hysterectomy, if appropriate, will help save lives. Triple P procedure has been recently developed as the conservative surgical alternative for women with abnormal invasion of the placenta and has been shown to significantly reduce the blood loss and to reduce inpatient stay.

[HELLP syndrome]. / Zespól HELLP.

HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) is a relatively rare complication of pregnancy. It usually develops in the IIId trimester or after delivery. HELLP syndrome is associated with increased maternal (placental abruption, disseminated intravascular coagulation, hepatic hematomas and rupture, and acute kidney injury) and neonatal (prematurity, low birth weight) risk complications. In this article the diagnosis, clinical picture and treatment of this disease have been shortly reviewed.

The BRAzil MAGnesium (BRAMAG) trial: a randomized clinical trial of oral magnesium supplementation in pregnancy for the prevention of preterm birth and perinatal and maternal morbidity.

BACKGROUND: Preterm birth is the leading cause of infant mortality globally, including Brazil. We will evaluate whether oral magnesium citrate reduces the risk of placental dysfunction and its negative consequences for both the fetus and mother, which, in turn, should reduce the need for indicated preterm delivery. METHODS/DESIGN: We will complete a multicenter, randomized double-blind clinical trial comparing oral magnesium citrate 150 mg twice daily (n = 2000 women) to matched placebo (n = 1000 women), starting at 121/7 to 206/7 weeks gestation and continued until delivery. We will include women at higher risk for placental dysfunction, based on clinical factors from a prior pregnancy (e.g., prior preterm delivery, stillbirth or preeclampsia) or the current pregnancy (e.g., chronic hypertension, pre-pregnancy diabetes mellitus, maternal age > 35 years or pre-pregnancy maternal body mass index > 30 kg/m2). The primary perinatal outcome is a composite of preterm birth < 37 weeks gestation, stillbirth > 20 weeks gestation, neonatal death < 28 days, or SGA birthweight < 3rd percentile. The primary composite maternal outcome is preeclampsia arising < 37 weeks gestation, severe non-proteinuric hypertension arising < 37 weeks gestation, placental abruption, maternal stroke during pregnancy or ≤ 7 days after delivery, or maternal death during pregnancy or ≤ 7 days after delivery. DISCUSSION: The results of this randomized clinical trial may be especially relevant in low and middle income countries that have high rates of prematurity and limited resources for acute newborn and maternal care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02032186, registered December 19, 2013.

Smoking cessation in pregnancy.

More than 400,000 deaths occur per year in the United States that are attributable to cigarette smoking; the risks to the general public are widely known. The risk to women, especially those who are pregnant, is less commonly known. During pregnancy, smoking increases the risk of low birth weight infants, placental problems (previa and/or abruption), chronic hypertensive disorders, and fetal death. It is proposed that much of this happens because of vasoconstriction with decreased uterine blood flow from nicotine, carbon monoxide toxicity, and increased cyanide production. Infants of smoking mothers have increased risks, such as sudden infant death syndrome.

First trimester prediction of ischemic placental disease.

Ischemic placental disease is characterized by one or more of the clinical manifestations of preeclampsia, fetal growth restriction, and/or placental abruption, resulting in indicated preterm delivery. Since over half of the indicated preterm deliveries are due to ischemic placental disease, accurate early prediction of the disease is of paramount importance in developing prevention strategies. This review article focuses on studies that have used the first trimester aneuploidy screening timing window to predict those patients who later develop ischemic placental disease. Emphasis was given to studies originating from the Fetal Medicine Foundation because of their uniformity in definitions and expertise of the personnel who performed the ultrasound screening exams.

Prediction and prevention of ischemic placental disease.

Preeclampsia, intrauterine growth restriction (IUGR), and placental abruption are obstetrical conditions that constitute the syndrome of ischemic placental disease or IPD, the leading cause of indicated preterm birth and an important cause of neonatal morbidity and mortality. While the phenotypic manifestations vary significantly for preeclampsia, IUGR, and abruption, these conditions may share a common underlying etiology as evidenced by: (1) shared clinical risk factors, (2) increased recurrence risk across pregnancies as well as increased co-occurrence of IPD conditions within a pregnancy, and (3) findings that suggest the underlying pathophysiologic processes may be similar. IPD is of major clinical importance and accounts for a large proportion of indicated preterm delivery ranging from the periviable to late preterm period. Successful prevention of IPD and resultant preterm delivery could substantially improve neonatal and maternal outcomes. This article will review the following topics: (1) The complicated research literature on aspirin and the prevention of preeclampsia and IUGR. (2) Research evidence on other medical interventions to prevent IPD. (3) New clinical interventions currently under investigations, including statins. (4) Current clinical recommendations for prevention of ischemic placental disease.

Impact of the nitric oxide-donor pentaerythrityl-tetranitrate on perinatal outcome in risk pregnancies: a prospective, randomized, double-blinded trial.

Intrauterine growth restriction (IUGR) and preeclampsia (PE) are associated with impaired placentation. Patients who are at risk of developing both these disorders can be identified by abnormal uterine artery Doppler at mid-trimester pregnancy. Nitric oxide (NO)-donors like pentaerithrityl-tetranitrate (PETN) reduce the impedance in the uteroplacental vessels and possess protecting effects on the endothelium. We tested the effectiveness of the NO-donor PETN for secondary prevention of IUGR, PE, and preterm birth in pregnancies at risk. Some 111 women who presented with abnormal placental perfusion at 19-24 weeks of gestation (w.o.g.) were included into a prospective, randomized, placebo-controlled, double-blinded study. The primary endpoint was IUGR and/or perinatal death. Secondary endpoints were preterm birth, PE, and placental abruption. Pentaerithrityl-tetranitrate significantly decreased the risk for IUGR and/or perinatal death [adjusted odds ratio (OR) 0.410; 95% confidence interval, CI, 0.184-0.914] and for IUGR (adjusted OR 0.436; 95% CI 0.196-0.970). Preterm birth before 32 w.o.g. (adjusted OR 0.204; 95% CI 0.052-0.801) was reduced, but not the risk for PE. No placental abruption occurred in the PETN, but five occurred in the placebo group [corrected]. These results suggest that secondary prophylaxis of adverse pregnancy outcome might be feasible in pregnancies exhibiting abnormal placentation using PETN.

Optimal treatment of hypothyroidism associated with live birth in cases of previous recurrent placental abruption and stillbirth.

OBJECTIVE: To examine the clinical management of and placentas from pregnant women with hypothyroidism and obstetric history of recurrent stillbirth in order to identify possible etiologic mechanisms. METHODS: Two cases involving 26-year-old women with hypothyroidism and history of recurrent stillbirth are reported. Placentas from all of the women's pregnancies were compared in order to identify histologic similarities. RESULTS: In both cases, multifocal hemorrhagic infarctions and abruptions were seen, indicating progressive uteroplacental ischemic damage leading to stillbirth. Thrombophilia, infection, and diabetes tests were all negative. With meticulous monitoring and normalization of thyroid function by end of first/early second trimester in subsequent pregnancies, there were live births and no evidence of infarction on placental histology. CONCLUSION: The 2 reported cases raise the possibility of uteroplacental ischemia and placental abruption being mechanisms by which hypothyroidism can lead to stillbirth; they also highlight the potential of minimizing this risk via adequate levothyroxine treatment from early pregnancy.

Expectant management of severe preeclampsia remote from term: the MEXPRE Latin Study, a randomized, multicenter clinical trial.

OBJECTIVE: The objective of the study was to determine whether expectant management of severe preeclampsia prior to 34 weeks of gestation results in improved neonatal outcome in countries with limited resources. STUDY DESIGN: This was a randomized clinical trial performed in 8 tertiary hospitals in Latin America. Criteria of randomization included gestational age between 28 and 33 weeks' gestation and the presence of severe hypertensive disorders. Patients were randomized to steroids with prompt delivery (PD group) after 48 hours vs steroids and expectant management (EXM group). The primary outcome was perinatal mortality. RESULTS: A total of 267 patients were randomized, 133 to the PD group and 134 to the EXM group. Pregnancy prolongation was 2.2 days for the PD group vs 10.3 days for the EXM group (P = .0001). The rate of perinatal mortality (9.4% vs 8.7%; P = .81; relative risk [RR], 0.91; 95% confidence interval [CI], 0.34-1.93) was not improved with expectant management, and neither was the composite of neonatal morbidities (56.4% vs 55.6%; P = .89; RR, 01.01; 95% CI, 0.81-1.26). There was no significant difference in maternal morbidity in the EXM group compared with the PD group (25.2% vs 20.3%; P = .34; RR, 1.24; 95% CI, 0.79-1.94). However, small gestational age (21.7% vs 9.4%; P = .005; RR, 2.27; 95% CI, 1.21-4.14) and abruption were more common with expectant management (RR, 5.07; 95% CI, 1.13-22.7; P = .01). There were no maternal deaths. CONCLUSION: This study does not demonstrate neonatal benefit with expectant management of severe preeclampsia from 28 to 34 weeks. Additionally, a conservative approach may increase the risk of abruption and small for gestational age.

An ethical priority greater than life itself.

This article discusses a case in this issue of The Journal of Clinical Ethics by McCrary and colleagues, "Elective Delivery Before 39 Weeks' Gestation Reconciling Maternal, Fetal, and Family Circumstances," in which parents asked the medical team to deliver their fetus "early." The author discusses (1) the importance that parents have to a child when they are able to love the child, and how important it is for decision makers to consider this; (2) exceptional approaches that may enable parents to "change their minds"; and (3) substantive and procedural innovations that may help to prevent clinicians' views from playing too big a role and/or being arbitrary. The author concludes by describing how he felt when reading the case and uses this to illustrate how clinicians may benefit by assessing their feelings.

Elective delivery before 39 weeks' gestation: reconciling maternal, fetal, and family interests in challenging circumstances.

We present the case of a 36-year-old woman who has experienced three lost pregnancies; during the most recent loss, a full term pregnancy, she almost died from complications of placental abruption. She is now completing the 34th week of gestation and is experiencing symptoms similar to those under which she lost the previous pregnancy. Despite a lack of specific medical indications, the patient and her husband firmly but politely request that the attending obstetrician/perinatologist perform an immediate cesarean section in order to alleviate the couple's anxiety about possibly never having a family. Discussing the case are an experienced perinatologist, a neonatologist, a regional perinatal center coordinator, and a clinical ethicist.

Characterization of ovine utero-placental interface tensile failure.

Data on the strength of the utero-placental interface (UPI) would help improve understanding of the mechanisms of placental abruption (premature separation of the placenta from the uterus) during motor-vehicle crashes involving pregnant occupants. An ovine model was selected for study because like the human, its placenta has a villous attachment structure. Uteri with intact placentas were obtained from three sheep as by-products of another research study. The samples were harvested between 102 and 119 days of the 145-day gestational period. Rectangular specimens with areas measuring 15 mm × 5 mm were cut through the thickness of the placenta and uterus. Each subject provided eight samples, of which four were tested at a nominal strain rate of 0.10 strains/sec and the remainder was tested at a nominal strain rate of 1.0 strains/sec. Sutures were used to secure the uterine side of the specimens to the test fixture, while mechanical clamps were used to attach the placenta side. A FARO arm scanner recorded the initial geometry of the tissue, and a random dot pattern applied to the placenta and uterus tissue allowed visualization of displacement. For the structure of the UPI, mean tensile failure strain and standard deviations are 0.37 (0.11) and 0.37 (0.18) for the 0.10 and 1.0 strain rates, respectively (p-value = 0.970) while the associated failure stresses are 6.5 (1.37) and 15.0 (5.08) kPa, (p-value = 0.064). The results from sheep UPI testing provide the first estimate of the human UPI structural failure tolerance.

Clinical management and outcome of pregnancies complicated by previous abruption.

OBJECTIVES: We studied the clinical management and prognosis of pregnant women with a history of abruption, as well as the associated risk factors. METHODS: We reviewed the cases of 23 patients with a history of abruption and 66 patients with abruption. RESULTS: The recurrence rate of abruption was 4.3%. Intentional care prolonged gestational age in most patients. Although the incidence of abruption was low (0.44%), the consequences could be perinatal death and maternal disseminated vascular coagulation (DIC). CONCLUSION: To prevent abruption recurrence, careful monitoring during hospitalization is important. Both clinical findings and transabdominal echography are useful in diagnosing abruption.