Tocolytic Research Articles

Is the beta3-adrenoceptor (ADRB3) a potential target for uterorelaxant drugs?

The management of premature birth still remains unsatisfactory. Since the relative lack of efficiency and/or safety of current tocolytic agents have been highlighted, it is necessary to develop new uterorelaxant drugs deprived of important maternal and foetal side effects. Our work reported in this review focuses on a potential new target for tocolytic drugs, the β3-adrenoceptor (ADRB3). This third type of ADRB is shown to be present and functional in human myometrium. We demonstrated that ADRB3 agonists are able to inhibit in-vitro spontaneous contractions of myometrial strips, via a cyclic AMP-mediated pathway. Furthermore, we established that ADRB3 is the predominant subtype over the ADRB2 in human myometrium and that its expression is increased in near-term myometrium, compared to non-pregnant myometrium. Finally, we reported that contrary to ADRB2, the human myometrial ADRB3 is resistant to long-term agonist-induced desensitisation. These compelling data confirm the clinical potential interest of ADRB3 agonists in the pharmacological management of preterm labour.

Routine Cervical Length in Twins and Perinatal Outcomes

Close to half of twin gestations end before term, and more than 20% deliver before 34 weeks' gestation. The risk of preterm delivery (PTD) reportedly increases as cervical length (CL) decreases. Reports that PTD is more frequent when a cerclage is placed for cervical shortening prompts the question of whether routinely measuring CL alters the outcome of twin pregnancies. This retrospective review compared outcomes in twin gestations with, and those without a CL. Of 262 women enrolled in the study, 184 had CLs and 78 did not. Those with CLs were likelier to be older and they presented significantly earlier for their first ultrasound study. Similar numbers of women in the two groups had a history of PTD or two or more spontaneous abortions. A median of 4 CL measurements was made. No differences between the CL and no-CL groups were found with respect to gestational age at delivery, preterm labor, or PTD before 28, 34, or 37 weeks' gestation. Rates of spontaneous abortion before 24 weeks also were similar in the two groups, as were cervical risk factors. There were no significant differences in antepartum hospital admission, cerclage placement, or use of tocolytic agents. Women in the CL group were admitted for an average of 34.5 days, compared to 31.3 days for the no-CL group, a significant difference. Antepartum length of stay, however, did not correlate with the number of CLs. Neonatal outcomes including birth weight and admission to neonatal intensive care were comparable in the two groups. Logistic regression analysis, controlled for potential confounding factors, showed that antepartum admission was an independent risk factor for birth before 34 weeks' gestation. The odds ratio was 1.06, with a 95% confidence interval of 1.00-1.12. Routine measurements of CL did not substantially either maternal or neonatal outcomes in this study of twin gestations.

Randomized Double-Blind Placebo-Controlled Trial of Transdermal Nitroglycerin for Preterm Labor

Preterm birth before 37 weeks’ gestational age complicates more than 12% of pregnancies. Tocolytic therapy is intended to reduce neonatal deaths and illness by delaying birth, but current tocolytic agents are not very effective and, despite prolonging pregnancy, have failed to improve infant outcomes. There is evidence from both animal and human studies that glyceryl trinitrate (GTN, nitroglycerin) achieves tocolysis with few serious side effects. This multicenter Canadian trial enrolled 153 women in labor at 24-32 weeks’ gestation, based on 4 or more painful uterine contractions every 20 minutes and cervical change. Seventy-four women were randomized to receive a transdermal GTN patch, and 79 to receive a placebo patch. An additional patch was applied if uterine activity continued after 60 minutes and, after 24 hours, all patches were replaced with the same number for 24 hours longer. Patches were removed after 48 hours. The primary outcome was a composite of neonatal mortality and morbidity, the latter including chronic lung disease, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis. Baseline characteristics were comparable in the intervention and control groups. Treatment with GTN reduced the primary composite outcome significantly (relative risk [RR], 0.29; 95% confidence interval [CI], 0.08, 1.00). The risk difference was −0.10 (95% CI, −0.19, −0.01). The number needed to treat was 10 (95% CI, 5, 100). Births before 28 weeks’ gestational age were reduced, although not significantly (RR, 0.50; 95% CI, 0.23, 1.09). Pregnancies were prolonged by 7.2 days on average in the GTN group, also not a statistically significant change. Women given GTN had significantly more side effects (RR, 1.41; 95% CI, 1.06, 1.86). The commonest problem was headache, but in most cases it was not necessary to remove the patches. The investigators conclude that, in view of the substantial health care and societal costs of neonatal morbidity, treating women in preterm labor with transdermal GTN may yield major cost savings and longer-term health benefits.

Ex utero intrapartum treatment (EXIT), a resuscitation option for intra-thoracic foetal pathologies.

The ex utero intrapartum treatment (EXIT) procedure is designed to guarantee sufficient oxygenation for a foetus at risk of airway obstruction. This is achieved by improving lung ventilation, usually by establishing an airway during caesarean delivery whilst preserving the foetal-placental circulation temporarily. Indications for the EXIT procedure have extended from its original use in reversing iatrogenic tracheal obstruction in congenital diaphragmatic hernia to naturally occurring upper airway obstructions. We report our experience with a new and rarely mentioned indication for the EXIT procedure, intra-thoracic volume expansions. The elaboration of lowest risk scenarios through balancing risks with alternative options, foetal or neonatal intervention and coordination between professionals from various disciplines are the most important conditions for a successful EXIT procedure. The EXIT procedure requires a caesarean section that specifically differs from the traditional caesarean section during which uterine tone is maintained to minimize maternal bleeding. To guarantee foetal oxygenation during the EXIT procedure, profound uterine relaxation is desired. To gain time with optimal placental oxygenation in order to safely perform an airway intervention in a baby at risk of hypoxia may require deep inhalation anaesthesia and/or tocolytic agents. We review the EXIT procedure and present a case series from the University Hospital of Geneva that contrasts with the common indication for the EXIT procedure usually based on upper airway obstruction by its exclusive indication for intra-thoracic malformations/diseases.

Ex utero intrapartum treatment (EXIT), a resuscitation option for intra-thoracic foetal pathologies.

The ex utero intrapartum treatment (EXIT) procedure is designed to guarantee sufficient oxygenation for a foetus at risk of airway obstruction. This is achieved by improving lung ventilation, usually by establishing an airway during caesarean delivery whilst preserving the foetal-placental circulation temporarily. Indications for the EXIT procedure have extended from its original use in reversing iatrogenic tracheal obstruction in congenital diaphragmatic hernia to naturally occurring upper airway obstructions. We report our experience with a new and rarely mentioned indication for the EXIT procedure, intra-thoracic volume expansions. The elaboration of lowest risk scenarios through balancing risks with alternative options, foetal or neonatal intervention and coordination between professionals from various disciplines are the most important conditions for a successful EXIT procedure. The EXIT procedure requires a caesarean section that specifically differs from the traditional caesarean section during which uterine tone is maintained to minimize maternal bleeding. To guarantee foetal oxygenation during the EXIT procedure, profound uterine relaxation is desired. To gain time with optimal placental oxygenation in order to safely perform an airway intervention in a baby at risk of hypoxia may require deep inhalation anaesthesia and/or tocolytic agents. We review the EXIT procedure and present a case series from the University Hospital of Geneva that contrasts with the common indication for the EXIT procedure usually based on upper airway obstruction by its exclusive indication for intra-thoracic malformations/diseases.

The choice of a tocolytic for the treatment of preterm labor: a critical evaluation of nifedipine versus atosiban

Preterm birth is the major cause of neonatal mortality and morbidity in the developed world. The perfect tocolytic that is uniformly effective with complete fetomaternal safety does not exist. Tocolytic agents differ in cost, utero-specificity, safety, efficacy and whether they are licensed for use. The main three agents that are used worldwide are β-agonists, Ca2+ channel blockers and vasopressin/oxytocin receptor antagonists. β-Agonists are gradually being phased out of use and are being replaced by either nifedipine or atosiban. The evidence base for atosiban is strong but the evidence is of poor quality for nifedipine. The balance of evidence indicates that atosiban is as effective as nifedipine and more effective than β-agonists and is significantly safer than both. Atosiban was developed specifically to treat preterm labor, so the cost is higher than nifedipine or ritodrine. However, the cost of a course of atosiban (∼ £200) should not only be considered in comparison with other tocolytic agents but to other medical budgets (e.g., oncology, fertility, cardiology and psychiatry) and to the huge healthcare costs associated with the morbidity and mortality caused by preterm birth. Atosiban is a new advance in the management of spontaneous preterm labor.

A Novel Tocolytic Agent: Effects of Letrozole on Gestational Length and Parturition Time

The purpose of this study was to determine whether letrozole, a potent aromatase inhibitor, could prolong gestation and/or delay parturition in rats. Seventy-five rats were divided into five groups of 15 rats each. Group I and group II rats were administered letrozole orally at doses of 0.002 and 0.02 mg/kg/day from days 15 through 21 of pregnancy, respectively. Rats in group IA were administered a concomitant estradiol cyclopentylpropionate (ECP) injection on day 15 and 0.002 mg/kg letrozole in that same manner as for group I. Rats in group IIA were administered concomitant ECP on day 15 and 0.02 mg/kg letrozole in the same manner as for group II. The control group received sterile saline only. Study and control groups were compared with respect to gestational length, parturition time, fetal mortality rate, stillbirth rate, and fetal body weight. Oral administration of letrozole both at daily doses of 0.002 mg/kg/day (group I) and 0.02 mg/kg/day (group II) consistently prolonged gestation and parturition time. The values of stillbirth rate, fetal mortality rate, and fetal body weight of group I were similar to those in the control group; conversely, fetal mortality rate and stillbirth rate of group II were higher than those values in the control group, and fetal body weight of group II was lower than in the control group. It was observed that concomitant injection of ECP effectively reversed the deleterious effects of letrozole on gestational length, parturition time, fetal mortality rate, stillbirth rate, and fetal body weight. The results of this study indicate that the aromatase inhibitor letrozole can prolong gestation and delays parturition in rats. Its deleterious effects on parturition can be reversed by ECP injection.

Nifedipine-associated pulmonary complications in pregnancy

Pulmonary edema (PE) is a known side effect of tocolytic agents. Recently the first case of PE associated with oral nifedipine (Adalat Bayer Germany) was reported. Two cases are added; one is a twin gestation who presented at 31-6/7 weeks in labor with ruptured membranes (ROM). Forty hours after starting betamethasone antibiotics and 40-mg nifedipine every 6 h she developed dyspnea. Arterial blood gases (ABG) revealed Pa/O2=52mmHg and saturation=88%. Bilateral crackles were detected. Chest X-ray revealed mild haziness over the left lower lobe; nifedipine was discontinued. Oxygen facemask and 3 doses of 20-mg furosemide (Lasix; Sanofi-Aventis U.S.A.) resulted in mild improvement. One episode of 38.3 °C temperature was recorded 8 h after discontinuing nifedipine so a cesarean delivery was performed. The second patient presented at 27-5/7 weeks in labor. She received betamethasone penicillin and 40-mg nifedipine every 6 h. Twenty hours later she had ROM and a temperature of 38°C. On day 3 contractions intensified; nifedipine was discontinued and MgS/O4 was given for 3 h. Three hours later she developed cough and dyspnea. Bilateral fine crackles were noted. Mg level was 5.7 mg/ dl. ABG revealed Pa/O2=45mmHg and saturation=81%. Chest X-ray revealed congestion. Duplex scan of the lower extremities was negative. She received 5 doses of 40-mg furosemide but saturation remained between 77 and 84% despite oxygen nasal-cannula and therapeutic heparin. A cesarean delivery was done. Postoperative chest X-ray suggested hilar pneumonia. Saturation improved on day 2 postoperatively. (excerpt)

Antenatal exposure to magnesium sulfate and the incidence of patent ductus arteriosus in extremely low birth weight infants

Magnesium sulfate (MgSO(4)) is the most commonly used tocolytic agent in the US and is also employed as a prophylactic agent against seizures in pre-eclamptic women. MgSO(4) crosses the placenta and its concentration in the newborn usually exceeds that of maternal levels. The purpose of this study was to explore the relationship between antenatal exposure to MgSO(4) and the incidence of patent ductus arteriosus (PDA) in extremely low birth weight infants. A total of 954 neonates with birth weights between 500 and 1000 g, born at the University of Miami/Jackson Memorial Hospital between January 1995 and December 2004 and surviving for more than 3 days, were followed until death or discharge from the hospital. The incidence of PDA in infants exposed to MgSO(4) was compared with those not exposed and comparisons were also made between infants exposed to different maternal doses of MgSO(4). The incidence of PDA was significantly higher in the group of infants exposed to MgSO(4) compared with the unexposed control group (67 vs. 60%, P<0.018). When stratified by gestational age the differences were significant only in the group of infants with a gestational age of >or=26 weeks (58 vs. 49%, P<0.039). Logistic regression analysis to adjust for co-variables indicated an increased risk of PDA with higher doses of MgSO(4) (odds ratio 1.33 confidence interval (CI) 1.12 to 1.58, per 50 g of MgSO(4)). Antenatal exposure to MgSO(4) is associated with a higher risk of PDA in extremely low birth weight infants and this effect is more significant and dose-related in more mature infants.

The influence of interleukin-1β on oxytocin signalling in primary cells of human decidua

Objective Oxytocin (OT) and its corresponding receptor (OTR), synthesized within the pregnant uterus, play a key role in the process of (preterm) labor as part of a paracrine system that regulates symmetrical contractility. In the setting of intrauterine infection, a major cause of preterm labour and birth, decidua serves as a major source of cytokine production. The present study evaluates the time-dependent effect [0–24 h] of the inflammatory cytokine Interleukin-1β (IL-1β) treatment on OT signalling and OT stimulated prostaglandin release in primary cultures of human decidua. Study design Primary cultures of human decidua ( n = 6) were treated with IL-1β [5 ng/ml] for 0–24h and or indomethacin [100 μM] – an inhibitor of the prostaglandin synthesis – for 0–24 h or for 24 h. OT peptide expression, OTR binding, Inositol triphosphate production (IP 3), and arachidonic acid (AA) as well as prostaglandin (PGE 2) release were measured. Results IL-1β transiently reduced cytoplasmic OT peptide at 4–6 h of IL-1β incubation, while its secretion into the media was increased after 6 h of stimulation. The later was completely blocked by indomethacin. A decrease in OTR mRNA expression and a loss of OTR binding were detected after 8 h and 16 h of IL-1β treatment, respectively. IL-1β also decreased IP 3 production and AA release, but significantly enhanced OT mediated PGE 2 production. This effect was completely suppressed by the cyclooxygenase-2 (COX-2) inhibitor NS-398. Conclusion Our data suggest, that IL-1β indirectly increases OT secretion in primary cultures of human decidua in a time dependent fashion through the production of prostaglandins through COX-2 and that this increase in OT peptide may secondarily down-regulate the OTR and its signalling cascade. These findings might explain the poor effectiveness of oxytocin receptor antagonists as tocolytic agents in the setting of intrauterine infection.

Use of barusiban in a novel study design for evaluation of tocolytic agents in pregnant and neonatal monkeys, including behavioural and immunological endpoints

The oxytocin receptor antagonist barusiban, currently being developed for treatment of preterm labour, was investigated in pregnant cynomolgus monkeys with a 9-month postnatal follow-up of their offspring. The nature of barusiban, its indication, and the potential exposure of pre- and postnatal infants entailed the design of a unique protocol to investigate all aspects of maternal and offspring well-being. Barusiban was administered to the mothers from gestation day 85 until delivery with daily subcutaneous dosages up to 2.5 mg/kg body weight/day. There were no test article-related effects seen in the mothers at any time during the study. The postnatal examination of offspring included routine toxicological parameters, as well as specialised investigation of the immune, cardiovascular, renal and central nervous systems, including a full behavioural assessment. A full pathology examination of offspring was performed at the end of the 9-month postnatal period. No adverse infant findings occurred.

Feasibility of a randomized controlled trial testing nifedipine vs. placebo for the treatment of preterm labor

Nifedipine is believed to be a superior tocolytic agent on the basis of efficacy and side-effect profile, but was never prospectively evaluated in a placebo-controlled randomized clinical trial (RCT). In our study, we sought to identify limitations in participation for a would-be RCT comparing nifedipine to placebo. A prospective feasibility study was conducted at Ste-Justine Hospital, a tertiary care center, on women between 24 and 34 weeks' gestation, presenting to the labor and delivery room with obstetrical complaints. Patient information was collected and would-be participants were identified on the basis of pre-established clinical and ultrasound criteria as well as on willingness to participate, as determined by the study research nurse. During a 6-month period, 483 women presenting with signs and symptoms of preterm labor (PTL) were eligible for further evaluation. A total of 321 (66.5%) women were excluded for obstetrical and medical reasons whereas 125 (25.9%) did not meet strict inclusion criteria (cervical length <25 mm or positive fetal fibronectin). When using strict criteria, only 37 women (7.6%) were found to be eligible for study participation. Subject willingness to participate as assessed by the research nurse was 50%. If adhering to strict inclusion/exclusion criteria, the feasibility of an appropriately sampled RCT testing tocolytic therapy against a placebo would require a large concerted multicenter effort to meet sample size demands.

Cardiopulmonary Bypass In Pregnancy: An Experience Of Three Different Clinical Scenarios

Since foetal mortality is extremely high, open heart surgeries during pregnancy should be tried with extreme caution. Some deviation from routine cardiopulmonary bypass protocols like higher perfusion flow, pressure and arterial oxygen tension, use of Tocolytic agents might result in improved foetal survival though maternal survival seems to depend on cardiac disease per se than on cardiopulmonary bypass. Foetal bradycardia is the earliest indication of foetal distress and must be aggressively managed.

Nifedipine is the most cost effective tocolytic

Nifedipine is the most cost effective tocolytic

The cost of preterm birth: the low cost versus high value of tocolysis

The consequences of preterm birth (PTB), to the individual and society at large, remain a major financial and personal burden. Babies born at the limits of viability, who survive, often have major neurological impairments, such as cerebral palsy, developmental delay and blindness. The cost of initial hospitalisation is more than $200,000 for each birth but takes no account of future costs once they leave the hospital. The major morbidities associated with extreme prematurity are respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH) and necrotising enterocolitis (NEC). With advancing gestational age at birth, the financial costs and morbidity associated with these conditions decrease. The major morbidities (RDS, IVH and NEC) are rare by 34 weeks of gestation, with the exception of RDS, which complicates 7% of deliveries at this gestational age. While the vast majority of infants survive the first year of life, the infant mortality rate is markedly increased by three- to five-fold even for the mildly preterm infants, as compared with that of the term infants. Neonates born after 34 completed weeks of gestation rarely have mortality or major morbidity, but the financial costs remain significant ($7000 per case), and efforts to prevent delivery at this gestational age are probably indicated. Economic costs associated with PTB include the cost of initial hospitalisation, the cost of any chronic diseases resulting from the prematurity and social costs including loss of gainful employment by a family member taking care of the infant or child and loss of potential future earnings of the affected child. Antenatal steroids, if given to the mother at least 48 hours prior to a PTB, have shown significant reductions in RDS, IVH and NEC. Efforts to prevent, or avoid, PTB include the use of tocolytic agents which have been shown to prolong gestation for a minimum of 48 hours, or longer in some cases. The range of tocolytic agents used to delay or prevent PTB work through many different pathways, with varying degrees of success. Which tocolytic agent to use depends on many factors including underlying maternal status, gestational age of the fetus and documented efficacy of agent used.

Clinical practice evaluation of atosiban in preterm labour management in six European countries

Objective To evaluate the efficacy and safety of early administration compared with standard administration of atosiban, when predefined eligibility criteria were met.Design A prospective, open‐label, randomised clinical trial. Women were randomised to receive atosiban either immediately (early) or when specified criteria, in terms of duration/frequency of uterine contraction or status of cervical dilation/effacement, were fulfilled (standard).Setting Carried out at 105 centres in six European countries.Population Pregnant women admitted to hospital in threatened preterm labour between 24 and 34 weeks of gestation, comprising a subgroup of women enrolled in the Tractocile Efficacy Assessment Survey in Europe (TREASURE) clinical experience review.Main outcome measures Efficacy was defined as the successful delay of delivery with no alternative tocolytic agent for 48 hours.Results More women in the early group remained undelivered at 48 hours with no alternative tocolytic agent compared with those who received atosiban when specified criteria were fulfilled (88.9 versus 76.1%; P = 0.03). Safety was comparable between the groups. There were no statistical differences in maternal, fetal or neonatal adverse events between the early and standard atosiban arms.Conclusions The use of atosiban was effective for the delay of preterm labour and presented no safety concerns irrespective of the time it was administered.

‘Normal’ pregnancy with adverse events on initial tocolytic treatment

Preterm birth is never low risk and there are advantages gained by prolonging gestation even at relatively advanced stages of pregnancy. This means that high-value treatments should not just be reserved for high-risk pregnancies. Some women treated with tocolytics will experience adverse events, and some adverse events are particularly associated with different classes of tocolytic agents. Cardiovascular adverse events are particularly common with beta-agonists and there have been several maternal deaths from pulmonary oedema as a result of beta-agonist use for tocolysis. Calcium channel blockers are often associated with maternal hypotension, and a number of case studies reporting serious adverse events have been reported. The aim of this case study is to discuss what can be done if a patient experiences adverse events with tocolytics, and suggests approaches to continuing patient management and implications for obstetric practice.

Magnesium sulfate suppresses inflammatory responses by human umbilical vein endothelial cells (HuVECs) through the NFκB pathway

Dysfunctional endothelial cell activation and cytokines are implicated in preterm labor, a condition commonly treated with the tocolytic agent, magnesium sulfate (MgSO4). Based on recent findings showing the inflammatory effects of magnesium deficiency, we examined the effect of MgSO4 on human umbilical vein endothelial cell (HuVEC) inflammatory responses in vitro. HuVECs isolated from term umbilical cords were incubated with MgSO4 prior to stimulation with lipopolysaccharide (LPS) and then assessed for endothelial cell activation. Endothelial cell supernatants were assayed for inflammatory mediator production (interleukin-8; IL-8), and endothelial cell-associated intercellular adhesion molecule (ICAM-1) expression was determined. In the absence of LPS stimulation, MgSO4 had no effect on HuVEC responses. Treatment of HuVECs with MgSO4 prior to LPS stimulation inhibited inflammatory mediator production (p<0.05) and cell adhesion molecule expression (p<0.05) in a dose-dependent manner. Mechanistic studies showed that MgSO4 reduced NFκB nuclear translocation and protected cytoplasmic IκBα from degradation in LPS-treated HuVECs. In conclusion, MgSO4 inhibits endothelial cell activation, as measured by levels of IL-8 and ICAM-1 expression, via NFκB. Our results support the hypothesis that MgSO4 treatment may function as an anti-inflammatory agent during preterm labor.

Adverse maternal and neonatal outcome of prolonged course of magnesium sulfate tocolysis

Magnesium sulfate continues to be widely used as a tocolytic agent despite a paucity of evidence supporting its use. Many practitioners use prolonged courses of magnesium sulfate, sometimes for months. This study was conducted to determine maternal and neonatal outcome of patients exposed to prolonged tocolytic magnesium sulfate. A retrospective review of maternal and neonatal charts (1995-2003) of pregnancies that received tocolytic magnesium sulfate. Cases who received magnesium sulfate >48 h (n=78) were compared to controls who received it < or =48 h (n=77) for maternal side effects and neonatal outcome. Cases were more likely to be nulliparous (55.1% versus 37.7%, p=0.044), multiple gestations (33.3% versus 10.4%, p=0.001), and of lower gestational age (29.0+/-3.9 versus 30.5+/-3.8 weeks, p=0.017) compared to controls. The median magnesium sulfate infused was 154 (78-5,500) versus 54 (8-86) g (p<0.001) and the highest maternal magnesium level was 6.5+/-1.7 versus 5.6+/-1.9 mg/dl (p=0.002) in cases and controls, respectively. Cases were more likely to have > or =1 adverse side effect (30.8% versus 15.6%, p=0.045). The median neonatal magnesium level was significantly higher in cases (3.3 (1.4-7.2) versus 2.6 (1.1-5.2) mg/dl, p=0.016); however, neonatal mortality and other neonatal morbidity rates were similar in both groups. Abnormal bone mineralization was encountered in 3 neonates (cases). Maternal morbidity rate is higher with prolonged intake of tocolytic magnesium sulfate compared to < or =48-h regimen. Despite similar neonatal morbidity and mortality rates, bone demineralization in the neonates may be encountered.

Acute pulmonary edema during tocolytic therapy with nifedipine

Calcium channel blockers are becoming more popular as first-line tocolytic agents. Serious side effects have rarely been reported and involved mainly intravenous use of nicardipine. We report the first case of acute pulmonary edema following tocolytic oral nifedipine. Possible contributing factors are mentioned.