Korean Mothersafe Center 10th Anniversary: Outcome and Future Prospects

PURPOSE@#The purpose of this report is to organize the history of Korean Mothersafe, a professional teratology information center. Throughout its domestic and international activities, Mothersafe has firm role to write journals and books, to provide counseling, to run educational courses on maternal and fetal toxicology, and so on. This paper delineates the achievements in last ten years and discusses the vision of Mothersafe.@*METHODS@#In order to formulate the accomplishments of Korean Mothersafe, the volume of counseling calls are carefully reviewed by their contents, counselees, and the consultation results, etc. Textbooks and journals based on the data from Mothersafe are evaluated. Other roles of the Mothersafe, such as hosting symposium and running public programs are also noted.@*RESULTS@#Korean Mothersafe provided 76,555 counseling to 45,933 expectant women and 30,622 breast-feeding women. The database has total 52,130 enrollments from 2010 to 2019. A total of 33 papers are published regarding medication, alcohol, smoking, radiation, etc. A specialized book on maternal-fetal toxicology was published and teratology part of obstetrics textbook was updated. Education programs and symposiums were held and primary care programs for expectant parents are run by Mothersafe.@*CONCLUSION@#Korean Mothersafe has contributed to safe environments for numerous pregnant and breast-feeding women regarding medication, drinking, smoking, and other hazardous substances. The huge database provided evidence for researches, textbooks and seminars, etc. Korean Mothersafe is now facing a new challenge to go forward through social dynamics with many issues regarding prevention and continuance of pregnancy, abortion, and so on.

Evaluation of nausea and vomiting in pregnancy using the Pregnancy-Unique Quantification of Emesis and Nausea scale in Korea

OBJECTIVE: Severity of nausea and vomiting of pregnancy (NVP) is associated with adverse pregnancy outcomes and poorer quality of life (QOL). The aim of this study was to evaluate the severity of NVP and maternal well-being status using the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scale in a Korean population. METHODS: A total of 527 pregnant women who were receiving prenatal care at 4 hospitals were asked to participate in the study between January 2015 and June 2015. The severity of NVP was evaluated by the PUQE scale and maternal well-being status was evaluated using the visual analogue scale (VAS). Statistical analyses were performed to determine the risk factors associated with NVP and the associations between the severity of NVP and QOL. RESULTS: Among the 472 eligible pregnant women, 381 (80.7%) were suffering from NVP during pregnancy. No significant differences (P>0.05) were observed in any of the variables between the 2 study groups, with the exception of smoking, alcohol consumption, and history of NVP. NVP history was found to be the most powerful risk factor (adjusted odds ratio, 11.6; 95% confidence interval, 4.7–28.7). The correlation coefficient (r) between the VAS scores of maternal well-being status and PUQE severity was −0.25 (r 2=0.062; P-< 0.001). CONCLUSION: In this study, an explicit decline in maternal well-being status was observed according to severity of NVP. The PUQE scale may be of help to clinicians, healthcare providers, and researchers because of its simplicity and usefulness as a tool for NVP evaluation.

Isotretinoin exposure in pregnant women in Korea

OBJECTIVE: Isotretinoin is a notorious teratogen otherwise used for the treatment of acne vulgaris. Some countries, including those in North America and the European Union, implemented the pregnancy prevention program (PPP); however, no PPP has yet been established in South Korea. So the aim of this study was to evaluate the rate of pregnant women exposed to isotretinoin among the callers of the Korean Mother Safe Counseling Center. METHODS: This is a prospective cohort study. We evaluated the demographic characteristics, obstetric history, and isotretinoin exposure of pregnant women based on the mother safe registry from April 2010 to July 2016. RESULTS: Among 22,374 callers, 650 (2.9%) pregnant women were exposed to isotretinoin. The mean age was 29.0±4.4 years in the isotretinoin-exposed group and 32.0±4.2 years in the unexposed group (P < 0.001). Moreover, the incidence of pregnancies within 30 days after isotretinoin discontinuation or during isotretinoin intake was 78.9% (513/650). The median duration of isotretinoin exposure was 18 (1–4,231) days. Furthermore, from 2011 to 2015, the incidence of isotretinoin exposure was 2.9±1.2 pregnancies per 10,000 births in South Korea. CONCLUSION: Approximately 80% of pregnant women are exposed to isotretinoin within the recommended 30 days of contraception or during pregnancy. Therefore, the PPP has to be established in South Korea.

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.

Changes in biochemical markers of bone turnover and bone mineral density during pregnancy and postpartum in korean women / 대한산부인과학회지

OBJECTIVE: To show the patterns of changes in biochemical markers of bone turnover and ultrasound bone mineral density (BMD) during pregnancy and postpartum in Korean women. METHODS: We conducted a prospective study between February 2004 and February 2005. Forty-one healthy singleton pregnant women were included. We used quantitative ultrasonography for BMD measurement which is advantageous to pregnant women because it is radiation-free and it provides very accurate BMD that correlates highly with BMD measured by conventional dual energy x-ray absorptiometry. We measured marker of bone resorption (beta-Crosslaps), bone formation [total alkaline phosphatase (ALP), osteocalcin (OC)], total calcium, phosphorus and parathyroid hormone (PTH) during and after pregnancy. RESULTS: During pregnancy, BMD slightly decreased in the third trimester. Bone resorption marker (beta-Crosslaps) increased steadily during pregnancy and immediate postpartum. Markers of bone formation (ALP, osteocalcin) increased from late pregnancy. Total calcium decreased slightly as bone resorption peaks in second trimester. PTH and phosphorus increased steadily throughout pregnancy and postpartum. CONCLUSION: Pregnancy is characterized by high bone turnover in Korean women with resorption preceding formation.

The association between polymorphisms of beta-adrenoceptors and preeclampsia

PURPOSE: The beta-adrenoceptors are pharmacologically classified into beta1-, beta2- and beta3-adrenoceptor. The gene of each subtype has polymorphisms related to their function (beta1-adrenoceptor: Ser49Gly, beta2- adrenoceptor: Gln27Glu, beta3-adrenoceptor: Trp64Arg). The objectives of this study were to analyse the allelic and genotypic distribution of the representative polymorphism of beta-adrenoceptors in preeclampsia and to investigate whether combined genotype of beta-adrenoceptors may be associated with preeclampsia. METHODS: Blood samples were collected from a Korean population (159 preeclamptic pregnancies and 168 normotensive pregnancies). The beta1-, beta2- and beta3-adrenoceptor genotypes was determined using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There were no differences in allelic and genotypic distribution of beta1- and beta2-adrenoceptor polymorphisms between the two groups. However, the Arg allele of beta3-adrenoceptor polymorphism were more frequent in preecalmpsia than in controls (P<0.05, OR=1.57, 95% CI=1.01-2.46). Moreover, prevalence of genotype carrying heterozygote of beta3-adrenoceptor polymorphism was increased in preeclampsia compared with controls (P<0.05, OR 1.76, 95% CI 1.06-2.92). When combination of the three polymorphisms were evaluated, pregnancies with the particular combined genotype that is consisted of heterozygote of beta1-, beta3-adrenoceptor and wild homozygote of beta2-adrenoceptor (Ser/Gly, Gln/Gln, Trp/Arg), showed a significant increase in the risk of preeclampsia (P<0.05, OR=3.01, 95% CI 1.12-8.08). CONCLUSION: A particular combined genotype (Ser/Gly, Gln/Gln, Trp/Arg) of - adrenoceptors was associated with the risk of preeclampsia.

The effects of epidural analgesia on labor progress and perinatal outcomes / 대한산부인과학회지

OBJECTIVE: We evaluated the effects of epidural analgesia on labor progress and perinatal outcomes in nulliparous women. METHODS: Between June 2004 and December 2004, we included total one hundred and thirty-two normal near term nulliparous women in early spontaneous labor or rupture of membranes for a prospective analysis. Patients were divided into those who received epidural analgesia (study group n=66) and those who did not (control group n=66). In order to evaluate the effects of epidural analgesia on labor progress, we compared the duration of active phase of labor and second stage of labor, cervical dilatation on admission, Bishop score and labor interval between the groups. We also compared perinatal outcomes between the two groups. RESULTS: The duration of active phase of labor was 4.7+/-2.0 hours in the study group and 3.6+/-1.9 hours in the control group showing a statistically significant prolongation in the duration of active phase of labor and significant slowing in the rate of cervical dilatation (p<0.05). The second stage of labor was also prolonged slightly in the study group (65.1+/-39.0 minutes) compared to the control group (54.1+/-33.5 minutes) but no statistical significance was noted. There was no significant difference in perinatal outcomes. CONCLUSION: Epidural analgesia may prolong active phase of labor. Therefore, we should always consider the effect of epidural analgesia before we decide to perform cesarean section.

Placental apoptotic change in 2nd trimester and full-term of normal pregnancies / 대한산부인과학회잡지

OBJECTIVE: The study aims were to demonstrate apoptosis in the placenta of normal pregnancy, and to identify its change and quantify its incidence by gestational age. METHODS: Placenta samples were collected from 25 normal full-term pregnancies and 20 second trimester pregnancies undergoing termination due to medical and social reasons. Hematoxylin and eosin staining and TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) staining were used to quantify the incidence of apoptosis and the electron microscopy was used to confirm it. Mann-Whitney U test and ANOVA test were used for statistical analysis. RESULTS: 1. Apoptosis was demonstrated by variable cytopathologic methods, and especially TUNEL staining and electron microscopy are found to be confirmatory methods. 2. In TUNEL staining, quantification of apoptosis was as follows: 2nd trimester (n=20) 1.05+/-0.69, full- term (n=25) 1.92+/-1.00. The incidence of apoptosis was significantly higher in full-term than in 2nd trimester (p0.05, Mann-Whitney U test). 4. There was no statistical significance in the incidence of apoptosis by maternal age, parity, cause of termination during 2nd trimester, and mode of delivery in each group. 5. In the electron microscopy, apoptotic cells were observed to have membrane blebbing, loss of microvilli, chromatin condensation and localization in the border of nuclear membrane, and cell shrinkage and increase in granularity. This method was conformatory in identifying apoptosis. CONCLUSION: Placental apoptosis increased significantly with increased gestational age, and this result suggests that it may play a role in the normal development and aging of the placenta.

A Case of Phlegmon caused by Chronic Pelvic Inflammation mimiking Pelvic Malignancy / 대한산부인과학회잡지

Pelvic inflammatory disease (PID) is a common disease associated with gynecologic infection, occurring mainly in fertile women. We report a case of phlegmon caused by chronic PID mimicking pelvic malignancy in a 39-year-old woman. The patient suffered from chronic pelvic pain, intermittent fever, and dysuria. A palpable lower abdominal mass was associated with progressive weight loss. A pelvic MRI revealed a 9x8x7cm sized, ill-defined soft tissue mass in the right pelvic cavity. On exploratory laparotomy, the pelvic mass was severly adhesed to the small intestine, mesentery, and urinary bladder. An incisional biopsy of the pelvic mass was performed. Histologically, the pelvic mass was composed of inflammed fibrous tissue with granulation tissue proliferation. The patient was treated with metronidazole and ciprofloxacin for two weeks. Fever and abdominal pain were relived. On a follow up abdomino-pelvic CT, the pelvic mass was not visible. Awareness of such an unusual case of chronic PID mimicking pelvic malignancy will facilitate a more accurate diagnostic approach for a variety of pelvic mass lesion.

A Case of Phlegmon caused by Chronic Pelvic Inflammation mimiking Pelvic Malignancy / 대한산부인과학회잡지

Pelvic inflammatory disease (PID) is a common disease associated with gynecologic infection, occurring mainly in fertile women. We report a case of phlegmon caused by chronic PID mimicking pelvic malignancy in a 39-year-old woman. The patient suffered from chronic pelvic pain, intermittent fever, and dysuria. A palpable lower abdominal mass was associated with progressive weight loss. A pelvic MRI revealed a 9x8x7cm sized, ill-defined soft tissue mass in the right pelvic cavity. On exploratory laparotomy, the pelvic mass was severly adhesed to the small intestine, mesentery, and urinary bladder. An incisional biopsy of the pelvic mass was performed. Histologically, the pelvic mass was composed of inflammed fibrous tissue with granulation tissue proliferation. The patient was treated with metronidazole and ciprofloxacin for two weeks. Fever and abdominal pain were relived. On a follow up abdomino-pelvic CT, the pelvic mass was not visible. Awareness of such an unusual case of chronic PID mimicking pelvic malignancy will facilitate a more accurate diagnostic approach for a variety of pelvic mass lesion.

Surgical Management of Ovarian tumors in Pregnancy: Laparoscopy versus Laparotomy / 대한산부인과학회잡지

OBJECTIVE: To evaluate the benefits of laparoscopic surgery compare with laparotomy in the surgical management of adnexal tumors during pregnancy. METHODS: Operating time, hospital stays, complications and pregnancy outcome were analyzed in 18 patients who underwent laparoscopic surgery and 30 patients who underwent laparotomy due to adnexal tumors discovered during pregnancy at Chungnam National University Hospital from January 1993 to June 2000. RESULTS: Mean age of the patients was 27.1 years and mean gestational age was not significantly different between the two groups. Tumor size was larger in laparotomy group (8.4 vs 6.4 cm in diameter). Unilateral salpingo-oophorectomy was most common operative procedures and cystic teratoma was most common histologic findings in both groups. Operating time was not significantly different between the two groups. Blood loss (43.2 vs 18.3 mL) and hospital stay (7.1 vs 5.7 days) was significantly less in laparscopy group. CONCLUSIONS: Laparoscopic surgery may be an effective treatment of adnexal tumors during pregnancy.

The clinical impact of absent or reversed end-diastolic velocity in the umbilical artery before the 34th week of pregnancy / 대한산부인과학회잡지

OBJECTIVE: To investigate the clinical impact of absent or reversed end-diastolic (ARED) umbilical artery flow detected before the 34th week of pregnancy in high-risk pregnancies. METHODS: Fifty-eight singleton pregnant women with high-risk factors were included in this retrospective study. Based on the umbilical artery Doppler finding, pregnant women were divided into 3 groups: group 1 (12 subjects) with normal Doppler systolic/diastolic (S/D) ratios; group 2 (30 subjects) with significant abnormal umbilical artery S/D ratios, and group 3 (16 subjects) with ARED flow in the umbilical artery between the 25+0 and 33+6 gestational weeks. Incidence of intrauterine growth retardation (IUGR) and pregnancy-induced hypertension, detection week, diagnosis-to-delivery interval, birth weight and gestational ages at delivery, Apgar scores, emergency cesarean section, neonatal intensive care unit (NICU) admission, admission-to-discharge interval, perinatal mortality (PNM) and morbidity, and neonatal morbidity were registered. Perinatal outcomes were assessed. The data was analyzed using the Mann-Whitney U-test and X-square test. A significant difference was considered present if p was<0.05. RESULTS: The PNM in group 3 in the study was 25% (4/16). Sixteen had ARED flow. Our study shows that fetuses with ARED flow tend to be more severely growth-retarded. Our results also show ARED flow to be associated with poor perinatal outcome. There was a higher incidence of cesarean section for fetal distress, neonatal intensive care unit admission, and lower Apgar scores. Birth weight and gestational age at delivery were lower. The diagnosis-to-delivery interval was shorter. The admission-to-discharge interval was longer. CONCLUSION: An early ARED finding before the 34th week in the umbilical artery is a very serious sign of likely fetal compromise. The perinatal mortality and morbidity rate were high, and there was evidence of acute or chronic hypoxia in most fetuses. It is an indication that extremely careful surveillance should be followed but not necessarily an indication for an emergency delivery.