Effect of Sustained Uterine Compression versus Uterine Massage on Blood Loss after Vaginal Delivery: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to compare the effectiveness of sustained uterine compression versus uterine massage in reducing blood loos after a vaginal delivery. STUDY DESIGN: This was a prospective randomized trial conducted at the American University of Beirut Medical Center (AUBMC) between October 2015 and October 2017. Inclusion criteria were women with a singleton pregnancy at ≥36 weeks of gestation, with less than three previous deliveries, who were candidates for vaginal delivery. Participants were randomized into two groups, a sustained uterine compression group (group 1) and a uterine massage group (group 2). Incidence of postpartum hemorrhage (blood loss of ≥500 mL) was the primary outcome. We assumed that the incidence of postpartum hemorrhage at our institution is similar to previously published studies. A total of 545 women were required in each arm to detect a reduction from 9.6 to 4.8% in the primary outcome (50% reduction) with a one-sided α of 0.05 and a power of 80%. Factoring in a 10% dropout rate. Secondary outcomes were admission to intensive care unit (ICU), postpartum complications, drop in hemoglobin, duration of hospital stay, maternal pain, use of uterotonics, or of surgical procedure for postpartum hemorrhage. RESULTS: A total of 550 pregnant women were recruited, 273 in group 1 and 277 in group 2. There was no statistically significant difference in baseline characteristics between the two groups. Type of anesthesia, rate of episiotomy, lacerations, and mean birth weight were also equal between the groups. Incidence of the primary outcome was not different between the two groups (group 1: 15.5%, group 2: 15.4%; p = 0.98). There was no statistically significant difference in any of the secondary outcomes between the two groups, including drop in hemoglobin (p = 0.79). CONCLUSION: There was no difference in blood loss between sustained uterine compression and uterine massage after vaginal delivery. KEY POINTS: · Transabdominal uterine compression and uterine massage are appropriate to prevent postpartum hemorrhage.. · No significant difference in blood loss or maternal discomfort observed between the two techniques.. · Both methods are equally effective and either one can be used based on provider preference..

A qualitative study of women and partners from Lebanon and Quebec regarding an expanded scope of noninvasive prenatal testing.

BACKGROUND: In the near future, developments in non-invasive prenatal testing (NIPT) may offer couples the opportunity to expand the range of genetic conditions tested with this technology. This possibility raises a host of ethical and social concerns, such as the type of information (medical vs. non-medical information) that couples might be exposed to and how this might complicate their informed decision-making. Currently, only limited research, mainly carried out in western countries, was conducted on women's and partners' views regarding the potential expansion of NIPT. METHODS: This study used semi-structured interviews with pregnant women and their partners to explore their views on future potential NIPT applications such as non-medical sex selection and non-medical traits, paternity testing, and NIPT use for fetal whole genome sequencing (FWGS). It was conducted in Lebanon and Quebec, as case studies to explore the impact of cultural differences on these views. RESULTS: We found no differences and many similarities when comparing the perceptions of participants in both contexts. While couples in both settings disapproved of the use of NIPT for non-medical sex selection and non-medical traits such as physical characteristics, they were near-unanimous about their support for its use for paternity testing in specific cases, such as legal doubts or conflicts related to the identity of the father. Participants were more ambivalent about NIPT for Fetal Whole Genome Sequencing. They supported this use to detect conditions that would express at birth or early childhood, while objecting to testing for adult-onset conditions. CONCLUSIONS: These results can further inform the debate on the future uses of NIPT and future policy related its implementation.

Implementation challenges for an ethical introduction of noninvasive prenatal testing: a qualitative study of healthcare professionals' views from Lebanon and Quebec.

BACKGROUND: The clinical introduction of non-invasive prenatal testing for fetal aneuploidies is currently transforming the landscape of prenatal screening in many countries. Since it is noninvasive, safe and allows the early detection of abnormalities, NIPT expanded rapidly and the test is currently commercially available in most of the world. As NIPT is being introduced globally, its clinical implementation should consider various challenges, including the role of the surrounding social and cultural contexts. We conducted a qualitative study with healthcare professionals in Lebanon and Quebec as case studies, to highlight the relevance of cultural contexts and to explore the concerns that should be taken into account for an ethical implementation of NIPT. METHODS: We conducted semi-structured interviews with 20 healthcare professionals (HCPs), 10 from each country, practicing in the field of prenatal screening and follow up diagnostic testing, including obstetricians and gynecologists, nurses, medical geneticists and, genetic counselors. We aimed to 1) explore HCPs' perceptions and views regarding issues raised by NIPT and 2) to shed light on ways in which the introduction of the same technology (NIPT) in two different contexts (Lebanon and Quebec) raises common and different challenges that are influenced by the cultural norms and legal policies in place. RESULTS: We identified challenges to the ethical implementation of NIPT. Some are common to both contexts, including financial/economic, social, and organizational/ educational challenges. Others are specific to each context. For example, challenges for Lebanon include abortion policy and financial profit, and in Quebec challenges include lobbying by Disability rights associations and geographical access to NIPT. CONCLUSIONS: Our findings highlight the need to consider specific issues related to various cultural contexts when developing frameworks that can guide an ethically sound implementation of NIPT. Further, they show that healthcare professional education and training remain paramount in order to provide NIPT counseling in a way that supports pregnant women and couples' choice.

Intravenous Oxytocin Use to Decrease Blood Loss during Scheduled Cesarean Delivery: A Randomized Double-Blinded Controlled Trial (OXYTRIAL).

Objective The objective of this study was to determine the optimal dose of intravenous oxytocin administered during cesarean delivery (CD) to decrease the amount of blood loss. Methods Out of a total of 226 women presenting for CD, 189 patients were randomized into three groups by a computer-generated random number sequence table. Low-risk women with singleton term pregnancies undergoing scheduled CD were assigned to receive 20, 30, or 40 units (U) of oxytocin diluted in 500 mL of lactated Ringer solution intraoperatively. The primary outcome was the change in hemoglobin from pre-CD to post-CD. Results Overall, 63 women were assigned to each group. The primary outcome which was the drop in hemoglobin (1.4 ± 1.1 g/dL, 1.1 ± 0.8 g/dL, 1.0 ± 1.1 g/dL; p = 0.097) and the total calculated blood loss (798.6 ± 298.3 mL, 794.4 ± 313.5 mL, 820.2 ± 316.2 mL; p = 0.893) were not significantly different among the study groups. The incidence of intraoperative hypotension, postoperative systolic, and diastolic blood pressure changes was similar across the groups. Conclusion The amount of blood loss during CD was not significantly different among the three groups, thus the lowest dose of oxytocin infusion (20 U in 500 mL of lactated Ringer solution) seems to be an appropriate regimen.

Recurrent twin pregnancy, with the second a heterotopic pregnancy, following clomiphene citrate stimulation: an unusual case and a review of the literature.

Multiple gestations are on the rise with the advent of artificial reproductive technologies. Even with ovulation induction using clomiphene citrate alone, the twinning rate can reach up to 9 percent. We report a case of recurrent twin gestation after treatment with clomiphene citrate, with the second pregnancy being heterotopic. We also review, using Medline and PubMed, previously reported cases of recurrent twin gestation after treatment with clomiphene citrate published before June 2014. Patients undergoing ovulation induction for oligoovulation, anovulation, or unexplained infertility should always be counseled about the possibility of multiple gestation prior to the treatment including the probability, although low, of a heterotopic pregnancy.

Guillain-Barre Syndrome With Concomitant Severe Preeclampsia: A Case Report.

With an estimated 100,000 new cases yearly worldwide, Guillain-Barre syndrome (GBS) is the most common cause of flaccid paralysis. GBS is exceedingly rare in pregnancy and carries high maternal and fetal risk. We report a case of a 38-year-old essential primigravida who presented at 38 weeks six days gestational age with ascending paraplegia progressing to dysarthria, dysphagia, and facial weakness. A clinical diagnosis of GBS was made in an outside institution, supported by elevated protein on lumbar puncture. During the antepartum period, a diagnosis of gestational hypertension progressed to preeclampsia with severe features when a sudden rise in liver function tests occurred. The patient underwent an uneventful planned cesarean delivery but could not be extubated due to respiratory failure. After a 20-day critical care admission, she was extubated and had an improvement in neurologic status to near her baseline.

Vaginoscopic resection of vaginal septum.

We report the resection of a vaginal septum while preserving the virginity of a 12-year-old girl with Herlyn-Werner-Wunderlich Syndrome (HWWS) having a didelphys uterus, obstructed hemivagina, and an ipsilateral renal agenesis with follow-up at 18 months. Successful resection of the vaginal septum with conservation of the hymenal ring and complete drainage of both the hematocolpos and the hematometra were achieved. Cyclic dysmenorrhea and pelvic pain were completely resolved on follow-up visits at 4, 6, and 18 months. Office hysteroscopy performed during the last follow-up visit revealed a patent vaginal vault without evidence of adenosis or recurrence of the vaginal septum. Vaginoscopy is a safe, convenient, and efficient diagnostic and therapeutic modality that can be used in the management of patients with an obstructed hemivagina. It maintains the patient's virginity and it is useful in patients with a restrictive vaginal opening or narrow vaginal canal. Furthermore, the hysteroscopic excision of the vaginal septum offers minimal risk of recurrence of the septal defect.

Practice patterns of obstetric care in twin gestations: the value of MFM consultation.

OBJECTIVES: To evaluate the practice patterns among Lebanese obstetricians regarding obstetric care of twins and to compare selected practice patterns between general obstetricians and maternal fetal medicine physicians. METHODS: Questionnaires distributed during the annual meeting of the Lebanese Society of Obstetrics and Gynecology. RESULTS: Questionnaires were returned by 69.2% of the 296 physicians approached. Ten percent had fellowship training in Maternal Fetal Medicine (MFM). Thirty-nine percent perform cervical length measurement at 20-24 weeks of gestation and 34% recommend vaginal progesterone in case of a short cervix. When comparing selected practice patterns between MFM & general obstetricians, MFM specialists were less likely to perform cervical cerclage in the first trimester (5.9% versus 49%, p = .001), more likely to offer prenatal screening for aneuploidy (66.6% vs 46.4%, p = .03), less likely to use vaginal progesterone in the second trimester in the case of a short cervix (42.1% vs 61.8%, p = .04), less likely to perform serial ultrasound exam in the third trimester to assess fetal growth (50% vs 78%, p = .005) and more likely to deliver monoamniotic twins at 32-34 weeks of gestation (55% vs 37%, p = .05). CONCLUSION: Because of the different background of the Lebanese physicians, MFM specialists are more likely to follow obstetric care guidelines in twin gestation.

The role of oxidative stress in the developmental origin of adult hypertension.

OBJECTIVE: To determine whether oxidative stress plays a role in the development of hypertension using a mouse model of fetal programming induced by endothelial nitric oxide synthase deficiency. STUDY DESIGN: Homozygous nitric oxide synthase knockout and wild type mice were cross-bred producing maternal (endothelial nitric oxide synthase+pat/-mat) and paternal (endothelial nitric oxide synthase+mat/-pat) heterozygous offspring. RNA from liver and kidney tissues of female pups were obtained at 14 weeks of age. Relative expression of the heat shock protein-B6, peroxiredoxin-3, superoxide dismutase-1, peroxisome proliferator-activated receptor gamma, nitric oxide synthase-1 and -2 were determined. RESULTS: In the kidneys, expression of nitric oxide synthase-2, peroxiredoxin-3, heat shock protein-B6, and superoxide dismutase-1 was up-regulated in endothelial nitric oxide synthase+pat/-mat but not in endothelial nitric oxide synthase+mat/-pat compared with wild type offspring. In the liver, there were no significant differences in the expression of nitric oxide synthase-1, nitric oxide synthase-2, peroxiredoxin, superoxide dismutase-1, or peroxisome proliferator-activated receptor gamma; however, heat shock protein-B6 was down-regulated in both heterozygotes offspring compared with wild type. CONCLUSION: The intrauterine environment alters oxidative pathways gene expression in the kidneys of offspring, which may be a mechanism in the development of adult hypertension.

Ectopic pregnancy in a uterine perforation site.

Uterine perforation can occur following first-trimester abortion or more commonly postpartum after evacuation of retained placental tissues. We report a case of a pregnancy at the site of a recent uterine perforation. Possible mechanisms of this rare condition and different therapeutic options are mentioned.

MR imaging in the triage of pregnant patients with acute abdominal and pelvic pain.

PURPOSE: To retrospectively assess the performance of MR imaging in the evaluation and triage of pregnant patients presenting with acute abdominal or pelvic pain. METHOD AND MATERIALS: MRI studies of pregnant patients who were referred for acute abdominal pain between 2001 and 2007 were included. MR images were retrospectively reviewed and compared with surgical and pathologic findings and clinical follow-up data. Analysis of imaging findings included evaluation of the visceral organs, bowel and mesentery, appendix (for presence of appendicitis), ovaries (detection and adnexal masses were evaluated), focal inflammation, presence of abscesses, and any other abnormal findings. RESULTS: A total of 118 pregnant patients were included. MR findings were inconclusive in 2 patients and were positive for acute appendicitis in 11 patients (n = 9 confirmed by surgery, n = 2 improved without surgery). One patient with inconclusive MR had surgically confirmed appendicitis; the other patient with inconclusive MR had surgically confirmed adnexal torsion. Other surgical/interventional diagnoses suggested by MR imaging were adnexal torsion (n = 4), abscess (n = 4), acute cholecystitis (n = 1), and gastric volvulus (n = 1). Two patients with MR diagnosis of torsion improved without surgery. One patient with MR diagnosis of abscess had biliary cystadenoma at surgery. The rest of the MR diagnoses above were confirmed surgically or interventionally. MR imaging was normal in 67 patients and demonstrated medically treatable etiology in 28 patients: adnexal lesions (n = 9), urinary pathology (n = 6), cholelithiasis (n = 4), degenerating fibroid (n = 3), DVT (n = 2), hernia (n = 1), colitis (n = 1), thick terminal ileum (n = 1), rectus hematoma (n = 1). Three of these patients had negative surgical exploration and one had adnexal mass excision during pregnancy. Other patients were discharged with medical treatment. The sensitivity, specificity, accuracy, positive predictive values (ppv), and negative predictive values (npv) of MR imaging for acute appendicitis, and surgical/ interventional diagnoses were 90.0% vs. 88.9%, 98.1% vs. 95.0%, 97.5% vs. 94.1%, 81.8% vs. 76.2%, 99.1% vs. 97.9%, respectively. CONCLUSION: MR imaging is an excellent modality for diagnosis of acute appendicitis and exclusion of diseases requiring surgical/interventional treatment. Therefore MR imaging is useful for triage of pregnant patients with acute abdominal and pelvic pain.

Splenic Artery Aneurysm (SAA) Rupture in Pregnancy: A Case Report of a Rare but Life-Threatening Obstetrical Complication.

This is the case of a 38 year-old Lebanese woman G2P1, history of previous cesarean section, presenting at 30+5 weeks of gestation with acute left-sided flank pain and a two-day history of chills and dysuria. In light of the clinical presentation, the patient was initially diagnosed with pyelonephritis and managed accordingly; however, her clinical status deteriorated with worsening hypotension and lethargy despite resuscitative measures and a normal abdominal ultrasound. Failure to revive the patient eventually led to a cardiac arrest for which a peri-mortem cesarean section was performed at bedside. Upon abdominal entry, an actively-bleeding ruptured splenic artery aneurysm (SAA) was identified, for which massive transfusion protocol was activated, and the patient was transferred to the operating room. The patient had a complicated postoperative course, the fetus was stillborn, and she was discharged home after 6 months of hospital stay. In view of the high mortality and morbidity associated with ruptured SAA in pregnancy, early recognition and prompt intervention are crucial for maternal and fetal benefit.

Accuracy of Pelvic Ultrasound in Diagnosing Adnexal Torsion.

Ovarian/adnexal torsion is a rather frequent occurrence in women of reproductive age group worldwide. Etiologies are quite diverse with ovarian lesions and corpus luteal cysts being the most two common. Pelvic or intravaginal ultrasound remains the first-line imaging modality used for diagnosis and evaluation of suspected ovarian/adnexal torsion. In this study, we have adopted a case-based statistical analysis to identify important sonographic markers and further evaluated their contribution in identifying ovarian torsion. Our study successfully determined the important sonographic markers. Our observation and analysis suggest that ovarian enlargement is the most sensitive marker. Ovarian edema was found to be the most specific marker to identify the ovarian torsion with higher level of accuracy and confidence. This pioneer study will provide valuable information and direction to the medical practitioners and radiologists for better diagnosis. Further studies with large sample size will help in establishing our findings universally.

Unexplained First Trimester Intrahepatic Cholestasis of Pregnancy: A Case Report and Literature Review.

Intrahepatic cholestasis of pregnancy (ICP) is a condition that usually affects the 3rd trimester-pregnant women and is associated with adverse pregnancy outcomes. We present a 31-year-old G2P1 patient with symptoms of ICP as early as 10 weeks of gestation (WG). Her pruritis was initially attributed to eczema. Due to the intensity of her discomfort and failure of topical treatment, ICP was suspected, total bile acid salt levels were taken and ursodeoxycholic acid was subsequently started at 18 WG. The patient was followed closely during her pregnancy to adjust the dose of the medication accordingly. Induction of labor was performed at 37 WG without complications. This case demonstrated the importance of clinical suspicion in the setting of such symptomatology in order not to miss or delay treatment of threatening conditions such as ICP.

Transgenerational effect of fetal programming on vascular phenotype and reactivity in endothelial nitric oxide synthase knockout mouse model.

OBJECTIVE: The objective of the study was to investigate the transgenerational effect of fetal vascular programming STUDY DESIGN: Homozygous NOS3 knockout and wild type controls (NOS3+/+WT) were cross-bred to obtain heterozygous offspring that developed in (KO-/-) mothers lacking a functional NOS3 (KOM) vs wild-type control mothers (KOP). The first-generation KOM(+/-) and KOP(+/-) female mice were then bred with WT(+/+) males to obtain a second generation (F2). F2 offspring were genotyped and WT(+/+)-F2 mice were then used for in vivo blood pressure and in vitro vascular reactivity studies. RESULTS: WT-F2 mice born to KOM mothers (KOM-F2WT) had significantly higher systolic blood pressure, mean arterial pressure, and pulse pressure, compared with WT-F2 born to KOP mothers. Male KOM-F2WT offspring had significantly increased response to phenylephrine (PE), compared with male KOP-F2WT. Male offspring had increased contractile responses to PE when compared with female. Acetylcholine responses were decreased in female KOM-F2WT, compared with female KOP-F2WT, but the difference was not statistically significant CONCLUSION: Our findings support a transgenerational effect of fetal programming on the vascular phenotype and suggest possible gender specific adaptation.

Prospective randomized trial of iliohypogastric-ilioinguinal nerve block on post-operative morphine use after inpatient surgery of the female reproductive tract.

OBJECTIVE: To determine the impact of pre-operative and intra-operative ilioinguinal and iliohypogastric nerve block on post-operative analgesic utilization and length of stay (LOS). METHODS: We conducted a prospective randomized double-blind placebo controlled trial to assess effectiveness of ilioinguinal-iliohypogastric nerve block (IINB) on post-operative morphine consumption in female study patients (n = 60). Patients undergoing laparotomy via Pfannenstiel incision received injection of either 0.5% bupivacaine + 5 mcg/ml epinephrine for IINB (Group I, n = 28) or saline of equivalent volume given to the same site (Group II, n = 32). All injections were placed before the skin incision and after closure of rectus fascia via direct infiltration. Measured outcomes were post-operative morphine consumption (and associated side-effects), visual analogue pain scores, and hospital length of stay (LOS). RESULTS: No difference in morphine use was observed between the two groups (47.3 mg in Group I vs. 45.9 mg in Group II; p = 0.85). There was a trend toward lower pain scores after surgery in Group I, but this was not statistically significant. The mean time to initiate oral narcotics was also similar, 23.3 h in Group I and 22.8 h in Group II (p = 0.7). LOS was somewhat shorter in Group I compared to Group II, but this difference was not statistically significant (p = 0.8). Side-effects occurred with similar frequency in both study groups. CONCLUSION: In this population of patients undergoing inpatient surgery of the female reproductive tract, utilization of post-operative narcotics was not significantly influenced by IINB. Pain scores and LOS were also apparently unaffected by IINB, indicating a need for additional properly controlled prospective studies to identify alternative methods to optimize post-surgical pain management and reduce LOS.

Antenatal antecedents and the impact of obstetric care in the etiology of cerebral palsy.

Cerebral palsy (CP) affects 2/1000 live-born children. Multiple antenatal factors, including preterm delivery, low birth weight, infection/inflammation, multiple gestation, and other pregnancy complications, are mostly associated with CP in both the preterm and term infant, with birth asphyxia playing a minor role. Owing to the increasing survival of the very preterm and very low birth weight infant secondary to improvements in neonatal and obstetric care, the incidence of CP may be increasing. The focus of this paper is to explore antenatal antecedents as etiologies of CP and the impact of obstetric care on the prevention of CP.

Cross-cultural perspectives on decision making regarding noninvasive prenatal testing: A comparative study of Lebanon and Quebec.

Noninvasive prenatal testing (NIPT), based on the detection of cell-free fetal DNA in maternal blood, has transformed the landscape of prenatal care by offering clinical benefits (noninvasive, high specificity and sensitivity, early detection of abnormalities) compared to existing prenatal screening tests. NIPT has expanded rapidly and is currently commercially available in most of the world. As NIPT spreads globally, culturally sensitive and ethically sound implementation will require policies that take into consideration the social and cultural context of prenatal testing decisions. In a Western context, the main ethical argument for providing access and public funding of prenatal tests is the promotion of reproductive autonomy (also referred to as "procreative liberty" and "reproductive freedom"), by enabling pregnant women and couples to access information about the fetus in order to choose a certain course of action for pregnancy management (continuation of pregnancy and preparation for birth or termination). So how is the framework of reproductive autonomy operationalized in non-Western cultural contexts? We used Quebec, Canada, and Beirut, Lebanon, for case studies to explore what ethical considerations related to reproductive autonomy should guide the implementation of the test in various cultural contexts. To answer this question, we conducted a qualitative study to (1) explore the perceptions, values, and preferences of pregnant women and their partners about NIPT and (2) examine how these values and perceptions influence reproductive autonomy and decision making in relation to NIPT in these two different cultural settings, Lebanon and Quebec. Our findings may guide health care professionals in providing counseling and in helping women and their partners make better informed prenatal testing decisions. Further, at a policy level, such understanding might inform the development of local guidelines and policies that are appropriate to each context.

To ignore or not to ignore placental calcifications on prenatal ultrasound: a systematic review and meta-analysis.

OBJECTIVE: The human placenta is known to calcify with advancing gestational age, and, in fact, the presence of significant calcifications is one of the components of grade III placenta, typical of late gestation. As such, the presence of significant placental calcifications often prompts obstetric providers to expedite delivery. This practice has been attributed, in part, to the presumed association between grade III placenta and adverse pregnancy outcomes. Such approach, however, can be the source of major anxiety and may lead to unnecessary induction of labor, with its associated predisposition to cesarean delivery as well as a myriad of maternal and neonatal morbidities. The objective of this study was to examine the association between grade III placental calcifications and pregnancy outcomes. MATERIALS AND METHODS: A systematic review of the literature was performed for studies evaluating the association between grade III placenta and a number of pregnancy outcomes, including labor induction, fetal distress (abnormal fetal heart tracing), low Apgar score (less than 7 at 5 min), need for neonatal resuscitation, admission to the Neonatal Intensive Care Unit, perinatal death, meconium liquor, and low birth weight. RESULTS: There was a five-fold increase in risk of labor induction with the presence of grade III placenta (OR 5.41; 95% CI 2.98-9.82). There was no association between grade III placenta and the incidence of abnormal fetal heart tracing (OR 1.62; 95% CI 0.94-2.78), low Apgar score of less than 7 at 5 min (OR 1.68; 95% CI 0.84-3.36), need for neonatal resuscitation (OR 1.08; 95% CI 0.67-1.75), and admission to the Neonatal Intensive Care Unit (OR 0.90; 95% CI 0.21-3.74). In turn, the incidence of meconium liquor was higher in the setting of grade III placentae (OR 1.68; 95% CI 1.17-2.39). Similarly, a positive association between grade III placental calcifications and low birth weight (OR 1.63; 95% CI 1.19-2.22) and perinatal death (OR 7.41; 95% CI 4.94-11.09) was identified. CONCLUSION: The study alerts us to a significant association between grade 3 placental calcifications and labor induction, although it demonstrates that these sonographic findings do not appear to predispose to fetal distress, low Apgar score, need for neonatal resuscitation, or admission to the NICU.

Effect of a previous pregnancy on vascular function in endothelial nitric oxide synthase 3 knockout mice.

OBJECTIVE: Nitric oxide deficiency has been implicated in adverse pregnancy outcomes. Mice that lack endothelial nitric oxide synthase (NOS3) have abnormal in vitro vascular reactivity. Our objective was to assess the effect of a previous pregnancy on the abnormal vascular function of NOS3 knockout mice. STUDY DESIGN: Carotid arteries from pregnant NOS3 knockout (NOS3(-/-KO)) and wild-type control mice (NOS3(+/+WT)) from first and second pregnancy were obtained for in vitro vascular reactivity studies. Vascular responses to cumulative concentrations of the vasoconstrictors phenylephrine, serotonin, and thromboxane and the vasorelaxants acetylcholine, sodium nitroprusside, and isoproterenol were determined. RESULTS: In the first pregnancy, contractile responses were exaggerated in the knockout animals, compared with the wild-type animals. However, the second pregnancy in knockout animals was associated with normalization of responses to phenylephrine and serotonin and increased responses to the endothelium-independent relaxants. CONCLUSION: The vascular function of NOS3 knockout mice improves with subsequent pregnancy becoming comparable to wild-type animals.