Validation of a Strict Obesity Definition Proposed for Asians to Predict Adverse Pregnancy Outcomes in Korean Pregnant Women

Background@#People are generally considered overweight and obese if their body mass index (BMI) is above 25 kg/m 2 and 30.0 kg/m 2 , respectively. The World Health Organization proposed stricter criteria for Asians (≥ 23 kg/m2 : overweight, ≥ 25 kg/m2 : obese). We aimed to verify whether this criteria could predict adverse pregnancy outcomes in Korean women. @*Methods@#We included 7,547 Korean women from 12 institutions enrolled between June 2016 and October 2018. Women with no pre-pregnancy BMI data, not Korean, or lost to followup were excluded, leaving 6,331. The subjects were categorized into underweight, normal, overweight, class I obesity, and class II/III obesity based on a pre-pregnancy BMI of < 18.5, 18.5–22.9, 23.0–24.9, 25.0–29.9, and ≥ 30.0 kg/m2 , respectively. @*Results@#Overall, 13.4%, 63.0%, 11.8%, 9.1%, and 2.6% of women were underweight, normal, and overweight and had class I obesity and class II/III obesity, respectively. In the multivariable analysis adjusted for maternal age, a higher BMI significantly increased the risk of preeclampsia, gestational diabetes, preterm delivery caused by maternal-fetal indications, cesarean section, large for gestational age, and neonatal intensive care unit admission. @*Conclusion@#Adverse pregnancy outcomes started to increase in those with a pre-pregnancy BMI ≥ 23.0 kg/m2 after adjusting for maternal age. The modified obesity criteria could help predict adverse pregnancy outcomes in Koreans.

Height of elevated fetal buttock for prediction of successful external cephalic version

14 cm, and HOB >7.8 cm were 10.80 (95% confidence interval [CI], 1.57–74.94), 5.26 (95% CI, 1.06–26.19), and 10.50 (95% CI, 1.03–107.12), respectively. Areas under the curve (AUCs) for AFI, HOB, and parity were 0.66 (95% CI, 0.54–0.78), 0.74 (95% CI, 0.64–0.85), and 0.69 (95% CI, 0.62–0.76), respectively. HOB had the largest AUC, but there were no significant differences among the AUCs of other factors. The cut-off value of HOB was 6 cm.CONCLUSION: This study showed that the AUC of HOB was greater than that of parity and AFI, although it was not statistically significant. As HOB is a noninvasive and comprehensive marker to predict successful ECV, consideration of HOB would be helpful before conducting ECV. Further studies are needed.

Progression to Gestational Diabetes Mellitus in Pregnant Women with One Abnormal Value in Repeated Oral Glucose Tolerance Tests

BACKGROUND: Women with one abnormal value (OAV) in a 100 g oral glucose tolerance test (OGTT) during pregnancy are reported to have an increased risk of adverse pregnancy outcomes. However, there is limited data about whether women with OAV will progress to gestational diabetes mellitus (GDM) when the OGTT is repeated. METHODS: To identify clinical and metabolic predictors for GDM in women with OAV, we conducted a retrospective study and identified women with OAV in the OGTT done at 24 to 30 weeks gestational age (GA) and repeated the second OGTT between 32 and 34 weeks of GA. RESULTS: Among 137 women with OAV in the initial OGTT, 58 (42.3%) had normal, 40 (29.2%) had OAV and 39 (28.5%) had GDM in the second OGTT. Maternal age, prepregnancy body mass index, weight gain from prepregnancy to the second OGTT, GA at the time of the OGTT, and parity were similar among normal, OAV, and GDM groups. Plasma glucose levels in screening tests were different (151.8±15.7, 155.8±14.6, 162.5±20.3 mg/dL, P<0.05), but fasting, 1-, 2-, and 3-hour glucose levels in the initial OGTT were not. Compared to women with screen negative, women with untreated OAV had a higher frequency of macrosomia. CONCLUSION: We demonstrated that women with OAV in the initial OGTT significantly progressed to GDM in the second OGTT. Clinical parameters predicting progression to GDM were not found. Repeating the OGTT in women with OAV in the initial test may be helpful to detect GDM progression.

Pregnancy Outcomes of Women Additionally Diagnosed as Gestational Diabetes by the International Association of the Diabetes and Pregnancy Study Groups Criteria

BACKGROUND: We investigated the pregnancy outcomes in women who were diagnosed with gestational diabetes mellitus (GDM) by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria but not by the Carpenter-Coustan (CC) criteria.METHODS: A total of 8,735 Korean pregnant women were identified at two hospitals between 2014 and 2016. Among them, 2,038 women participated in the prospective cohort to investigate pregnancy outcomes. Diagnosis of GDM was made via two-step approach with 50-g glucose challenge test for screening followed by diagnostic 2-hour 75-g oral glucose tolerance test. Women were divided into three groups: non-GDM, GDM diagnosed exclusively by the IADPSG criteria, and GDM diagnosed by the CC criteria.RESULTS: The incidence of GDM was 2.1% according to the CC criteria, and 4.1% by the IADPSG criteria. Women diagnosed with GDM by the IADPSG criteria had a higher body mass index (22.0±3.1 kg/m² vs. 21.0±2.8 kg/m², P<0.001) and an increased risk of preeclampsia (odds ratio [OR], 6.90; 95% confidence interval [CI], 1.84 to 25.87; P=0.004) compared to non-GDM women. Compared to neonates of the non-GDM group, those of the IADPSG GDM group had an increased risk of being large for gestational age (OR, 2.39; 95% CI, 1.50 to 3.81; P<0.001), macrosomia (OR, 2.53; 95% CI, 1.26 to 5.10; P=0.009), and neonatal hypoglycemia (OR, 3.84; 95% CI, 1.01 to 14.74; P=0.049); they were also at an increased risk of requiring phototherapy (OR, 1.57; 95% CI, 1.07 to 2.31; P=0.022) compared to the non-GDM group.CONCLUSION: The IADPSG criteria increased the incidence of GDM by nearly three-fold, and women diagnosed with GDM by the IADPSG criteria had an increased risk of adverse pregnancy outcomes in Korea.

Change in rates of prenatal tests for chromosomal abnormality over a 12-year period in women of advanced maternal age

OBJECTIVE: In 2007, the American College of Obstetricians and Gynecologists (ACOG) recommended that all pregnant women be offered screening or diagnostic tests for chromosomal abnormalities regardless of their age. Noninvasive prenatal testing (NIPT) for common chromosomal aneuploidies was introduced as a screening test in case of high-risk pregnancies. We assessed the rates of prenatal tests in women aged 35 years and older. METHODS: A retrospective study was conducted to compare the rates of amniocentesis, chorionic villus sampling (CVS), serum screening, and NIPT from January 2005 through March 2017 in women aged 35 years and older. We divided the initial 12 months after NIPT introduction into 4-month intervals, beginning in April 2016 through March 2017. RESULTS: The rates of amniocentesis were 56% before the ACOG statement, 38% between the ACOG statement and NIPT introduction, and 10% after NIPT introduction (P=0.001). The rates of CVS during the same periods were 0.5%, 2.1%, and 4.3% (P=0.016), respectively. The rates of serum screening were 44.2%, 61.3%, and 55.1% (P=0.049), respectively. During the 3 quarters after NIPT introduction, the rates of amniocentesis were 16.2%, 12.3%, and 7.3% (P=0.002), respectively; the rates of serum screening were 62%, 54%, and 46% (P=0.03), respectively; and the rates of NIPT were 19.9%, 30.3%, and 39.5% (P=0.007), respectively. The rates of CVS over the same periods were not significantly different. CONCLUSION: The ACOG statement and NIPT introduction significantly decreased the rate of amniocentesis in women of advanced maternal age. NIPT also reduced the rate of serum screening.

First trimester screening for trisomy 18 by a combination of nuchal translucency thickness and epigenetic marker level

PURPOSE: The aim of this study was to assess the diagnostic efficacy of noninvasive prenatal screening for trisomy 18 by assessing the levels of unmethylated-maspin (U-maspin) and fetal nuchal translucency (NT) thickness during the first trimester of pregnancy. MATERIALS AND METHODS: A nested case-control study was conducted using maternal plasma samples collected from 65 pregnant women carrying 11 fetuses with trisomy 18 and 54 normal fetuses. We compared the U-maspin levels, NT thicknesses, or a combination of both in the first trimester between the case and control groups. RESULTS: U-maspin levels and NT thickness were significantly elevated in the first trimester in pregnant women carrying fetuses with trisomy 18 when compared to those carrying normal fetuses (27.2 vs. 6.6 copies/mL, P<0.001 for U-maspin; 5.9 vs. 2.0mm, P<0.001 for NT). The sensitivities of the U-maspin levels and NT thickness in prenatal screening for fetal trisomy 18 were 90.9% and 90.9%, respectively, with a specificity of 98.1%. The combined U-maspin levels and NT thickness had a sensitivity of 100% in prenatal screening for fetal trisomy 18, with a specificity of 98.1%. CONCLUSION: A combination of U-maspin levels and NT thickness is highly efficacious for noninvasive prenatal screening of fetal trisomy 18 in the first trimester of pregnancy.

Fetal Programming and Adult Disease

Chronic diseases such as cardiovascular disease, type 2 diabetes, and hypertension are leading causes of death and disability worldwide. Evidence from epidemiological and experimental studies suggests that adverse exposure in uterus, particularly with regard to nutrition, increases the risk of chronic disease in adults. Nutritional programming is the process through which variation in the quality or quantity of nutrients consumed during pregnancy exerts permanent effects upon the developing fetus. Research on programming in relation to disease processes has been facilitated by the development of animal models that utilize restriction or over-feeding. Such studies have introduced the concept of developmental origins of health and disease (DOHaD). The underlying mechanisms of DOHaD remain an area of research interest and intense investigation. Although great strides have been made in identifying the putative concepts and mechanisms relating specific exposure in early life to the risk of developing chronic diseases in adult, many aspects of these associations remain unclear. This paper discusses the potential mechanisms behind the DOHaD as they relate to maternal nutrition and implications for future research and clinical practice.

Prediction and Prevention of Large for Gestational Age in Gestational Diabetes Mellitus / 대한주산의학회잡지

Gestational diabetes mellitus (GDM) is an important disease which complicates pregnant woman and fetus. Large for gestational age (LGA) is one of the primary complications and is closely associated with the hyperglycemia of pregnant woman. Although strict control of blood glucose can decrease the occurrence of LGA, the rate of LGA in GDM pregnancy is higher than that of normal pregnancy. Understanding of the difference of fetal growth between LGA and adequate for gestational age in GDM pregnancy and consideration about the time and marker for prediction and prevention of LGA in GDM pregnancy are helpful for prenatal care of GDM pregnancy. In this article, the prediction and prevention of LGA in GDM pregnancy will be discussed.

Observed frequency of fetal trisomy between 16 and 24 gestational weeks in pregnant women older than 34 years at delivery

PURPOSE: Increased maternal age is a major risk factor for chromosomal abnormalities. The maternal age-specific risk of fetal trisomy was theoretically calculated. We investigated the actual frequency of fetal trisomy between 16 and 24 gestational weeks in pregnant women over the age of 34 at delivery. MATERIALS AND METHODS: We retrospectively, over a four-year period, reviewed the medical records of women with singleton pregnancies that started their antenatal care before the 10th week of pregnancy. Pregnant women aged 34 to 45 years at the time of delivery were enrolled and divided into groups of one-year intervals. We investigated the frequency of Down syndrome and all trisomies as a function of the maternal age and compared with the theoretical maternal-age-specific risk. RESULTS: Of the 5,858 pregnant women enrolled in the study, the rate of trisomy 21 was 0.29% (17 cases). The observed frequencies of trisomy 21 in women with maternal ages of 35 years and 40 years were 1:1,116 and 1:141, respectively. The rate of all trisomies was 0.39% (23 cases). The observed frequencies of all trisomies in women with maternal ages of 35 years and 40 years were 1:372 and 1:56, respectively. CONCLUSION: The frequencies of Down syndrome and all trisomies were proportional to the maternal age. However, the observed frequencies of Down syndrome and all trisomies between the 16 and 24 gestational weeks were lower than the theoretical rates.

Gestational weight gain is an important risk factor for excessive fetal growth

OBJECTIVE: To estimate the odds ratio of prepregnant body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM) for excessive fetal growth, which we define as large for gestational age (LGA). METHODS: We included 16,297 women who delivered a live-born singleton baby at term. We fit logistic regressions to estimate the odds ratios of variables, including maternal age, parity, prepregnant BMI > or =23, GWG > or =15 kg, and GDM, for LGA. We classified GWG into four categories ( or =20 kg) and BMI into four categories (underweight, normal, overweight, and obese). After adjusting for age and parity, we analyzed the odds ratios of prepregnant BMI according to GWG between non-GDM and GDM women for LGA. RESULTS: The odds ratios of GWG > or =15 kg and prepregnancy BMI > or =23 for LGA were 2.40 (95% confidence interval [CI], 2.16-2.67) and 2.24 (95% CI, 1.99-2.51), respectively. The odd ratio of GDM was 1.37 (95% CI, 1.09-1.71). The risk of GDM women with normal/-overweight BMI and GWG or =15 kg might be a more important risk factor for LGA than either prepregnancy BMI > or =23 or GDM. Risk for LGA was highest in obese GDM women with GWG > or =15 kg.

A Prenatal Case of Paracentric Inversion of Chromosome 18, inv(18)(q21.1q22)

Paracentric inversion of chromosome 18 is a rare cytogenetic abnormality. The vast majority of paracentric inversions are harmless and the offspring of paracentric inversion carriers have only slightly elevated risks for unbalanced karyotypes. However, various clinical phenotypes are seen due to breakpoint variation or recombination. We report a prenatally detected case of familial paracentric inversion of chromosome 18, inv(18)(q21.1q22), with normal clinical features.

A Prenatal Case of Paracentric Inversion of Chromosome 18, inv(18)(q21.1q22)

Paracentric inversion of chromosome 18 is a rare cytogenetic abnormality. The vast majority of paracentric inversions are harmless and the offspring of paracentric inversion carriers have only slightly elevated risks for unbalanced karyotypes. However, various clinical phenotypes are seen due to breakpoint variation or recombination. We report a prenatally detected case of familial paracentric inversion of chromosome 18, inv(18)(q21.1q22), with normal clinical features.

Fetal Loss Rate after Mid-trimester Amniocentesis

PURPOSE: The aim of this study was to asses the fetal loss rate after mid-trimester amniocentesis. MATERIALS AND METHODS: This was a retrospective cohort study including singleton pregnant women who underwent mid-trimester amniocentesis at Cheil General Hospital from January 2008 through December 2010. The procedure-related fetal loss was defined as miscarriage within 2 weeks after amniocentesis. We evaluated the fetal loss rate within 2 weeks after amniocentesis and fetal loss rate before 24 gestational weeks. RESULTS: During the study period, a total of 4,356 singleton pregnant women underwent mid-trimester amniocentesis. A total of Five hundred ninety six women were excluded owing to follow up loss and termination of pregnancy due to abnormal karyotype or major anomaly. At our institute, the fetal loss rate within 2 weeks was 0.1% and before 24 gestational weeks was 0.3% after amniocentesis. CONCLUSION: The fetal loss rate after mid-trimester amniocentesis in our study is lower than previously reported rate. We suggest that amniocentesis is a safe procedure.

Analysis of Drug Counseling for Breastfeeding Mothers at the Korean Mothersafe Professional Counseling Center; 5 Years Experience / 대한주산의학회잡지

PURPOSE: There is a dearth of information on maternal drug exposure during lactation. The Korean Mothersafe Professional Counseling Center launched helpline to provide information and clinical consultation service on drug safety during lactation as well as in pregnancy. Here, we reviewed our 5 years' experience of counseling with drug exposed breastfeeding mothers. METHODS: The questionnaires were given to drug exposed breastfeeding mothers from January 2005 to April 2010 who contacted our helpline and follow-up survey data was collected by phone call. The questionnaires included lists of symptoms that exposed mothers experienced and that was observed in their infants, as well as demographic questions and questions about lactation. RESULTS: A total of 278 mothers completed the survey and lactational exposure was estimated. Majority of them reported that their infants and themselves never experienced serious side effects of drugs during lactation. Only 3 (1.1%) babies reported side effects and 20 (7.2%) mothers reported decreased production of breast milk. Two hundred thirty two (83.5%) mothers continued breastfeeding after counseling. Lactation was stopped temporarily in 20 (7.2%) mothers and permanently in 26 (9.3%) mothers. CONCLUSION: Most of the drugs exposed during lactation did not cause serious side effects to infants and mothers. As many drugs have inadequate data to assure safety, the clinician is left with a dilemma as to where the balance of risks and benefits lie with respect to the mother and her baby. The author expect that analyses of these counseling will contribute to provide practical answers to clinicians as well as exposed mothers and to establish correct breastfeeding practice.

Pregnancy Outcomes after Peri-conceptional Medication Exposure; 10 Years Experience: Study for Application of Reproductive Toxicity Information / 대한주산의학회잡지

PURPOSE: In Korea, pregnancy termination is frequently reported among women who took medications for an acute or chronic disease during pregnancy, for fear of teratogenic risk. We have previously shown that a service providing evidence-based information is helpful for women who week counseling to make a rational decision regarding their pregnancies. This study aimed to evaluate whether termination of pregnancy based on such perceptions, is justified using the 'DRug Exposure and risk Assessment in Moms' (DREAM) registry. METHODS: The study included 5,032 consenting pregnant women from the clinic and call center at the Korean Motherisk Program, from November 1999 to October 2008. The DREAM registry recorded the pregnancy outcomes (preterm birth, low birth weight, intrauterine fetal death, and congenital anomaly) of 3,328 women. RESULTS: Among women exposed to medications, time of exposure ranged from 3.5-4.6 weeks of gestation. There were 1,308 different drugs prescribed to these women. The drug most frequently prescribed was acetaminophen followed by chlorpheniramine maleate, and pseudoephedrine. There were 4.7% (n=156/3,328) women who underwent a voluntary abortion for fear of birth defects. We compared frequency of birth defects between exposed women and unexposed pregnant women in our institution during gestation. The frequency of major congenital malformations was 2.5% (n=74/2,977) in exposed group and 2.9% (n=75/2,573) in unexposed group (P=0.32). There was no statistically significant difference between exposed and control group in the rate of preterm births, intrauterine fetal death and low-birth weight babies. CONCLUSION: We did not observe increased risk of congenital malformations and adverse pregnancy outcomes in a population of pregnant women exposed to a variety of medications. Therefore these medications are not considered teratogen.

Effective Method for Extraction of Cell-Free DNA from Maternal Plasma for Non-Invasive First-Trimester Fetal Gender Determination: A Preliminary Study

PURPOSE: To find the most effective method for extraction of cell-free DNA (cf-DNA) from maternal plasma, we compared a blood DNA extraction system (blood kit) and a viral DNA extraction system (viral kit) for non-invasive first-trimester fetal gender determination. MATERIALS AND METHODS: A prospective cohort study was conducted with maternal plasma collected from 44 women in the first-trimester of pregnancy. The cf-DNA was extracted from maternal plasma using a blood kit and a viral kit. Quantitative fluorescent-polymerase chain reaction (QF-PCR) was used to detect the SRY gene and AMEL gene. The diagnostic accuracy of the QF-PCR results was determined based on comparison with the final delivery records. RESULTS: A total of 44 women were tested, but the final delivery record was only obtained in 36 cases which included 16 male-bearing and 20 female-bearing pregnancies. For the blood kit and viral kit, the diagnostic accuracies for fetal gender determination were 63.9% (23/36) and 97.2% (35/36), respectively. CONCLUSION: In non-invasive first-trimester fetal gender determination by QF-PCR, using a viral kit for extraction of cf-DNA may result in a higher diagnostic accuracy.

Pregnancy Outcomes after Conservative Treatment of Cervical Intraepithelial Lesions: Cold Knife Conization and Loop Electrosurgical Procedure / 대한주산의학회잡지

OBJECTIVE: In this study, we evaluated whether different methods of conization of the cervix were associated with an increased risk of adverse pregnancy outcomes in subsequent pregnancy. METHODS: A retrospective case-control study was conducted. The study group included women who had undergone cold knife conization (n=170) or a loop electrosurgical excision procedure (LEEP) (n=86) and then had subsequent singleton pregnancies. The control group (n=497) included women with no history of cervical surgery. The outcomes were spontaneous preterm delivery and various neonatal outcomes such as low birth weight (LBW) and perinatal mortality. RESULTS: Cold knife conization was associated with a significantly increased risk of preterm delivery less than 34 weeks (relative risk 4.9, 95% confidence interval 1.6-15.1), preterm delivery less than 28 weeks (7.6, 15-39.6), LBW (2.6, 1.2-5.8), and perinatal mortality (11.9, 1.3-107.6). LEEP was not associated with a increased risk of adverse pregnancy outcomes. CONCLUSION: Cold knife cone biopsy, but not LEEP of the cervix, is associated with an increased risk of preterm delivery less than 34 weeks of gestation and adverse neonatal outcomes. Clinicians counsel women appropriately before conservative treatment of cervical intraepithelial lesions.

Treatment outcome of uterine compression sutures for massive postpartum hemorrhage / 대한산부인과학회지

OBJECTIVE: Uterine compression sutures such as modified B-Lynch suture or multiple square-shaped sutures of uterine body are simple methods for control of postpartum hemorrhage refractory to medical treatment. We evaluated the treatment outcome and morbidity of uterine compression sutures and analyzed clinical findings of patients undergone uterine compression sutures and postpartum hysterectomy. METHODS: From January 2005 through December 2008, we retrospectively reviewed the medical records of patients undergone uterine compression sutures or postpartum hysterectomy. We analyzed success rates of preserving uterus of uterine compression sutures according to operative indications and mode of delivery and compared maternal characteristics, operative findings, morbidities and mortality with those of postpartum hysterectomy. RESULTS: The frequency of uterine compression sutures for control of massive postpartum hemorrhage was 0.24% (73/30,677). The success rates of preserving uterus were 85.1% in uterine atony, 80.9% in placenta previa, and 40.0% in placenta accreta (P=0.051). The rates of preserving uterus of uterine compression sutures after vaginal delivery and cesarean section were 50.0% and 82.6%, respectively (P=0.164). The frequencies of postoperative morbidities such as disseminated intravascular coagulation, pulmonary edema, ileus were not different between immediate hysterectomy and hysterectomy after uterine compression sutures. There was no maternal mortality. CONCLUSION: Uterine compression suture was successful method for control of postpartum hemorrhage resulting from uterine atony and placenta previa. We suggest the use of uterine compression sutures as the first-line operation for control of postpartum hemorrhage.

Analysis of the clinical characteristics and prognostic factors of ruptured hepatocellular carcinoma / 대한간학회지

BACKGROUND/AIMS: Spontaneous rupture of hepatocellular carcinoma (HCC) is a rare but life-threatening complication. Although the prevalence rate and mortality of HCC has been reportedly high in Korea, studies on ruptured HCC are limited. The aim of this study was to determine the clinical characteristics and prognostic factors of ruptured HCC. METHODS: Among 886 cases with HCC that had been diagnosed at Chonnam National University Hospital from January 2002 to December 2007, 62 cases (7.0%) with ruptured HCC were studied retrospectively regarding their clinical characteristics and prognostic factors. RESULTS: Transarterial embolization was performed in 56 cases (90.3%) to control bleeding, with a hemostasis success rate of 89.3%. The survival time after the rupture of HCC was 8.0+/-1.7 months (mean+/-SD), although it was longer in HCC cases that were first diagnosed in a ruptured state or ruptured with a small amount of bleeding than in those that ruptured during follow-up after diagnosis or with a large amount of bleeding, respectively. The 30-day mortality rate in patients with a ruptured HCC was 43.5%, and the early deaths were independently associated with the presence of hepatic encephalopathy (odds ratio, OR=44.7; 95% confidence interval, CI=1.9-1051.1; P=0.018), serum bilirubin >3.0 mg/dL (OR=36.7; 95% CI=1.3-1068.5; P=0.036), and the massive or diffuse type of tumor morphology (OR=53.5; 95% CI=3.0-964.2; P=0.007). CONCLUSIONS: The prognosis in patients with ruptured HCCs was poor with a 30-day mortality of 43.5%. The early deaths after the rupture of HCC were associated with elevated serum bilirubin levels, hepatic encephalopathy, and the massive or diffuse type of tumor morphology.

Fetal Anomaly and Pregnancy Outcomes after Exposure to Ibuprofen in First Trimester of Pregnancy / 대한주산의학회잡지

PURPOSE: Ibuprofen is a non steroidal anti-inflammatory drug used for treating fever and pain including headache, arthralgia, and back pain. There is scarce information on the safety of ibuprofen associated with fetal anomaly when used early in pregnancy. Epidemiology studies have suggested that use of NSAIDs, including ibuprofen, during pregnancy may increase the risk of cardiac defects and gastroschisis. The aim of the study was to evaluate fetal outcomes among pregnant women who were unintentionally exposed to ibuprofen in early pregnancy. METHODS: Total 381 pregnant women who were unintentionally exposed to ibuprofen during early pregnancy were prospectively followed up. In addition, 643 age and gravity matched pregnant women not exposed to any potential teratogenic agent during pregnancy were recruited as controls. Patients were followed-up until delivery or loss to follow-up. Newborns were examined in order to identify any major congenital malformation. RESULTS: Mean age of exposed women was 31.2+/-3.4 years, with a mean number of previous pregnancies of 2.3+/-1.2 and mean gestational weeks at exposure of 4.4+/-2.2. All gestations were confirmed by ultrasonography. Of exposed women, 17 (5.6%) had spontaneous abortions, 16 were on- going pregnancies, 1 had an intra-uterine fetal death, 21 artificial abortion and 55 cases were lost to follow-up. Therefore, 271 pregnancies unintentionally exposed to ibuprofen were evaluated, each delivering a singleton baby. Three babies had congenital anomalies: one had unilateral hydronephrosis, another baby was born with a unilateral inguinal hernia. The last baby was born with unilateral kidney dysplasia with megaureter. In the control group, 6 babies were born with major malformations [1.11% vs. 1.31% (P=0.552, OR: 0.841, 95% CI: 0.2 to 3.4)]. CONCLUSION: These preliminary results suggest that the ibuprofen may not be a major human teratogen.