Prevalence of FSH-R Asn680Ser and Ala307Thr receptor polymorphism and their correlation with ART outcomes among infertile Indian-Asian women-a prospective cohort study.

The present prospective cohort study evaluated the prevalence of FSH-R receptor Asn680Ser and Ala307Thr among infertile Indian women and the correlation of these polymorphisms with ART outcomes. Total 804 infertile and 209 fertile controls were enrolled for FSH-R analysis. Correlation of different genotypes with ovarian reserve markers, IVF parameters, and cumulative live birth rates (CLBR) was done among women undergoing IVF. In fertile controls, at 680 position GG (Ser/Ser) was the most common genotype; but among infertile women, all the genotypes were equally distributed. There was no significant difference in ovarian response parameters, oocyte yield, and CLBR among the three genotype groups. Empty follicle syndrome (EFS) was highest in women with AA or AG type at both positions. On categorisation of unexpected poor responders according to POSEIDON stratification; GG genotype at both positions had the lowest risk ratio of low-oocyte yield in ART cycles, but these differences were not statistically significant. This is the largest study from Indian ethnicity showing GG (Ser/Ser) genotype is most common among fertile women. The effect of FSH-R genotypes is very marginal on IVF parameters and is not reflected in CLBR. More prospective data may be required on the correlation of these genotypes with genuine EFS, thus stratifying the next cycles with self or donor oocytes. Routine genetic testing of FSH-R polymorphism should not be done except in a research setting. As both 680 and 307 positions are in linkage disequilibrium, only 680 position analysis may be done in a research setting.

Fetal Klippel-Trenaunay-Weber Syndrome: Antenatal Diagnosis and Postnatal Management.

Context: Klippel-Trenaunay-Weber syndrome (KTWS) is a rare disease characterized by a triad of venous malformations, vascular skin nevus and asymmetric hypertrophy of bone and soft tissue. The spectrum of disease in utero varies from asymptomatic nevus flammeus to life threatening complications like Kasabach-Merritt phenomena. Aim: The aim of this study was to review our experience of antenatal diagnosis of KTWS and it's postnatal management. Settings and Design: This was a retrospective observational study of all pregnant women who were antenatally diagnosed with KTWS and postnatally confirmed at a tertiary care center in north India between 2012 and 2021. Subjects and Methods: The electronic medical records were reviewed and data were collected regarding demographic information, obstetric history, clinical presentation, sonographic findings, mode of delivery, fetal outcome, and follow-up. Results: During the study period, four fetuses were diagnosed with KTWS on sonography. Three women were multigravida whereas one was a primigravida. Two women opted for medical termination of pregnancy and one each had liveborn child and an intra-uterine fetal death. KTWS was confirmed in all cases. The liveborn child underwent treatment for the vascular malformation and is alive at 4 years of age. Conclusions: This study attempts to add onto the available literature regarding the spectrum of prenatal presentations of KTWS. It emphasizes the importance of prenatal diagnosis and follow-up of the fetus/neonate.

Modeling of the As (III) adsorption using Fe impregnated polyethylene terephthalate char matrix: A statistical approach.

The present research aimed to analyse the impact of economical Fe impregnated polyethylene terephthalate (PET) char (PETC-Fe) for adsorption of As (III) through series of column experiments. For an inlet arsenite concentration of 1,000 µg/L, PETC-Fe exhibits excellent uptake capacity of 1,892 µg/g. Central composite design (CCD) in response surface methodology (RSM) was used to evaluate the influence of various process variables on the response function (breakthrough time) for optimization and assessment of interaction effects. The breakthrough time is more responsive to influent As (III) concentration and bed height than inlet flow rate, according to the perturbation plot. Adams-Bohart, Bed Depth Service Time (BDST) model, and Thomas models were used to model the dynamics of the adsorption system. The BDST model suited the experimental data well in the early part of the breakthrough curve, but there were minor variations over the breakpoints. Despite the fact that the experimental values and the data sets estimated using the Adams-Bohart model followed a similar pattern, they differed slightly. The PETC-Fe was found to be a sustainable and highly economical adsorbent, with a desorption performance of more than 97%, indicating the adsorbent's reusability. This adsorbent's excellent As (III) uptake capacity and regeneration performance imply that it might be used in industrial/domestic applications, and the information obtained could aid in future scaling up of the adsorption system.

Ovarian Reserve and Assisted Reproductive Technique Outcomes After Laparoscopic Proximal Tubal Occlusion or Salpingectomy in Women with Hydrosalpinx Undergoing in Vitro Fertilization: A Randomized Controlled Trial.

STUDY OBJECTIVE: To evaluate the outcomes of assisted reproductive technology (ART) after proximal tubal occlusion (PTO) or salpingectomy in patients with hydrosalpinx undergoing in vitro fertilization-embryo transfer (IVF-ET). DESIGN: Randomized controlled trial (Canadian Task Force classification I). SETTING: All India Institute of Medical Sciences, New Delhi, India. PATIENTS: A total of 165 patients were randomized and subsequently allocated to a PTO group (n = 83) or a salpingectomy group (n = 82). INTERVENTIONS: PTO and salpingectomy. MEASUREMENTS AND MAIN RESULTS: Following surgery, compared with the PTO group, the salpingectomy group showed significant decreases in the ovarian reserve parameters serum anti-Müllerian hormone (AMH; 3.7 ng/mL vs 2.6 ng/mL; p ˂ .001) and antral follicle count (AFC; 10.6 vs 8.6; p ˂ .001). The salpingectomy group also required a significantly higher dose of gonadotropins (3901 vs 3260; p ˂ .001) and more days of stimulation (11.3 vs 10.2; p ˂ .001) compared with the PTO group. The salpingectomy group had a significantly lower fertilization rate (0.74 vs 0.83; p ˂ .001) and a lower number of grade 1 embryos (4.1 vs 5.6; p = .02); however, there was no significant difference between the 2 groups with respect to rates of implantation (22.8% vs 23.7%; p = .87), clinical pregnancy (26.3% vs 33.7%, p = .25), live birth (27.5% vs 32.5%; p = .42), and miscarriage (4.7% vs 3.5%; p = .90) CONCLUSIONS: PTO is a superior to salpingectomy for the surgical management of patients with hydrosalpinx undergoing IVF-ET in terms of ovarian reserve. However, the 2 surgical techniques are associated with comparable pregnancy rates.

Paternal factors and embryonic development: Role in recurrent pregnancy loss.

The events occurring at the maternal-foetal interface define a successful pregnancy but the current paradigm has shifted towards assessing the contribution of spermatozoa for embryogenesis. Spermatozoa with defective DNA integrity may fertilise the oocyte but affect subsequent embryonic development. The present case-control study was conducted in male partners of couples experiencing recurrent pregnancy loss (RPL) to assess the gene expression of spermatozoal FOXG1, SOX3, OGG1, PARP1, RPS6, RBM9, RPS17 and RPL29. This was correlated with reactive oxygen species (ROS) levels and DNA Fragmentation Index (DFI). Semen samples were obtained from 60 cases and 30 fertile controls. Gene expression was done by qPCR analysis, and relative quantification was calculated by the 2-ΔΔCt method. Chemiluminescence and the sperm chromatin structure assay were used to measure the ROS and DFI levels respectively. FOXG1, OGG1, RPS6 and RBM9 were seen to be upregulated, while SOX3 and PARP1 were downregulated. Relative expression of SOX3, OGG1, RPS6 and RPS17 showed a significant difference between patients and controls (p < 0.05). RPL patients were seen to have high ROS (>27.8; p = 0.001) and DFI (>30.7; p < 0.0001) with respect to controls. Sperm transcript dysregulation and oxidative DNA damage can be "carried over" after implantation, thus affecting embryogenesis and health of the future progeny.

Fertility awareness and knowledge among Indian women attending an infertility clinic: a cross-sectional study.

BACKGROUND: To evaluate fertility knowledge and awareness among infertile women attending an Indian assisted fertility clinic and their understanding of the menstrual cycle, how age affects fertility and need for assisted fertility treatment. METHODS: A cross sectional study was conducted including 205 women seeking fertility treatment at an assisted reproductive unit between March 2017 to August 2017. Patients were interviewed with the help of structured questionnaire by a fertility counsellor. The previous studies were reviewed and a questionnaire was made according to our patient profile and sociodemographic characteristics. Knowledge and awareness was stratified according to socioeconomic status (SES). RESULTS: Most women (59%) were aged between 20 to 30 years indicating concern about their fertility and need for evaluation. More than half (63%) women were from the middle socio-economic strata. Knowledge about fertility and reproduction was low: 85% were not aware of the ovulatory period in the menstrual cycle, only 8% considered age more than 35 years as the most significant risk factor for infertility and most were unaware of when to seek treatment for infertility after trying for pregnancy. Less than half of women understood the need for assisted fertility treatment and donor oocytes in advanced age. CONCLUSIONS: Most Indian women across different SES are unaware of the effect of age on fertility. Targeted educational interventions are needed to improve knowledge regarding ideal age of fertility, factors affecting fertility potential and fertility options available for sub-fertile couples. Fertility counselling and information should be provided to young people at every contact with health care professionals.

Meditation & yoga: Impact on oxidative DNA damage & dysregulated sperm transcripts in male partners of couples with recurrent pregnancy loss.

Background & objectives: Recurrent pregnancy loss (RPL) is one of the devastating complications of pregnancy and current focus lies in addressing the management of paternal factors. Dysregulation in selective transcripts delivered to oocyte at fertilization can result in pregnancy losses and adversely affect embryogenesis. The objective of this study was to assess the effect of yoga-based lifestyle intervention (YBLI) on seminal oxidative stress (OS), DNA damage and spermatozoal transcript levels. Methods: The present study was a part of a prospective ongoing exploratory study and 30 male partners of couples with RPL were included from August 2016 to June 2017. Semen samples were obtained at baseline and at the end of YBLI (21 days). Gene expression analysis was performed by quantitative polymerase chain reaction on spermatozoal FOXG1, SOX3, OGG1, PARP1, RPS6, RBM9, RPS17 and RPL29. The levels of seminal OS and sperm DNA damage was assessed by measuring levels of reactive oxygen species (ROS) by chemiluminescence and DNA fragmentation index (DFI) by sperm chromatin structure assay. Results: SOX3, OGG1 and PARP1 were observed to be upregulated, while FOXG1, RPS6, RBM9, RPS17 and RPL29 showed downregulation. A significant reduction in ROS levels, an increase in sperm motility, sperm count (done twice) and a decrease in DFI was seen after YBLI. Interpretation & conclusions: Adopting YBLI may help in a significant decline in oxidative DNA damage and normalization of sperm transcript levels. This may not only improve pregnancy outcomes but also improve the health trajectory of the offspring.

Frontline use of bevacizumab in ovarian cancer: Experience from India.

Background: Ovarian cancer is the second most common gynaecological malignancy in India. Despite relatively high response rates to first-line carboplatin and paclitaxel-based chemotherapy in epithelial ovarian cancer (EOC), the majority of patients experience multiple relapses and finally become resistant. Vascular endothelial growth factor (VEGF) promotes progression of ovarian cancer. Bevacizumab, a recombinant humanized monoclonal antibody directed against VEGF-A is an anti-angiogenesis agent. Data on the use of bevacizumab for EOC from India are not available. We, therefore, studied the use of bevacizumab in ovarian cancer. Methods: In this prospective, non-randomized study, 10 patients who received bevacizumab were compared with 20 age- and stage-matched controls. After maximal surgical debulking, patients in the bevacizumab arm received bevacizumab 15 mg/kg i.v. on day 1 every 3 weeks followed by paclitaxel and carboplatin from cycle 1. After 6 cycles, bevacizumab was continued for 1 year. Controls received paclitaxel 1 75 mg/m2 and carboplatin only for 4-8 cycles. The outcome measures were adverse effects and progression-free survival. Results: Haematological toxicity (i.e. neutropenia, thrombocytopenia and anaemia) was similar in both arms. Hypertension (40% v. 10%, p = 0.04) and bleeding-related complications (50% v. 0%, p = 0.002) were more in the bevacizumab arm. However, gastrointestinal (GI) perforations were not increased. The median progression-free survival was similar in both arms; 26 months versus 21 months (p = 0.57). Conclusion: In this small group of patients, addition of bevacizumab increased the toxicity of chemotherapy.

A novel lung explant model for the ex vivo study of efficacy and mechanisms of anti-influenza drugs.

Influenza A virus causes considerable morbidity and mortality largely because of a lack of effective antiviral drugs. Viral neuraminidase inhibitors, which inhibit viral release from the infected cell, are currently the only approved drugs for influenza, but have recently been shown to be less effective than previously thought. Growing resistance to therapies that target viral proteins has led to increased urgency in the search for novel anti-influenza compounds. However, discovery and development of new drugs have been restricted because of differences in susceptibility to influenza between animal models and humans and a lack of translation between cell culture and in vivo measures of efficacy. To circumvent these limitations, we developed an experimental approach based on ex vivo infection of human bronchial tissue explants and optimized a method of flow cytometric analysis to directly quantify infection rates in bronchial epithelial tissues. This allowed testing of the effectiveness of TVB024, a vATPase inhibitor that inhibits viral replication rather than virus release, and to compare efficacy with the current frontline neuraminidase inhibitor, oseltamivir. The study showed that the vATPase inhibitor completely abrogated epithelial cell infection, virus shedding, and the associated induction of proinflammatory mediators, whereas oseltamivir was only partially effective at reducing these mediators and ineffective against innate responses. We propose, therefore, that this explant model could be used to predict the efficacy of novel anti-influenza compounds targeting diverse stages of the viral replication cycle, thereby complementing animal models and facilitating progression of new drugs into clinical trials.

Efficacy of metformin in improving glycaemic control & perinatal outcome in gestational diabetes mellitus: A non-randomized study.

BACKGROUND & OBJECTIVES: Gestational diabetes mellitus (GDM) can cause adverse perinatal outcome if not treated. Although insulin therapy has been the main treatment modality over decades but considering its cost and parenteral mode of administration, it does not seem to be appropriate, especially in low-resource settings. The objective of this study was to evaluate the role of metformin in GDM and know its efficacy as well as adverse effect on foetus and mother. METHODS: All pregnant women with GDM who were not controlled on medical nutrition therapy and required metformin therapy were included in the study. Careful monitoring of blood sugar was done. Development of any maternal or foetal complications and adverse effect were recorded. RESULTS: A total of 2797 pregnant women were screened, of whom 233 (8.3%) were found to have GDM. Of the 64 women with GDM (28.7%) who required metformin therapy, majority (93.8%) achieved blood sugar control, whereas three (4.7%) women failed. Caesarean section rate was 54 per cent, and 15.6 per cent neonates were large for gestational age. Only two (3.1%) women had gastrointestinal side effects which were minor and got resolved with time. No case of hypoglycaemia or perinatal mortality was reported. INTERPRETATION & CONCLUSIONS: Our findings indicate that metformin may be used as a safe and effective oral hypoglycaemic agent in GDM, especially in low-resource settings where cost, storage and compliance are logistic issues. However, long-term follow up studies are needed to solve issues related to its safety in pregnancy.

Comparative Study of Laparoscopic Abdominopelvic and Fallopian Tube Findings Before and After Antitubercular Therapy in Female Genital Tuberculosis With Infertility.

STUDY OBJECTIVE: To study the effect of antitubercular treatment (ATT) on the laparoscopic abdominopelvic and fallopian tube findings in female genital tuberculosis (FGBT). DESIGN: Prospective cohort (Canadian Task Force classification II2). SETTING: Tertiary referral center in northern India. PATIENTS: Fifty women with infertility and diagnosed with FGTB on laparoscopy, histopathology findings, or endometrial sampling (acid-fast bacilli culture, granuloma on histopathology, positive polymerase chain reaction). INTERVENTIONS: Diagnostic laparoscopy in all women diagnosed with FGTB before and after a 6-month course of ATT (2 months of rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by 4 months of rifampicin and isoniazid). All procedures were performed by the same surgeon between June 2012 and May 2014. MEASUREMENTS AND MAIN RESULTS: The mean patient age was 28.7 years, mean parity was 0.9, and mean body mass index was 23.6 kg/m(2). Infertility was seen in all 50 women (66% primary infertility, 34% secondary infertility), with a mean duration of 6.06 years. Abnormal laparoscopic findings of FGTB included tubercles in the pelvic peritoneum, fallopian tube, and ovary in 27 women (54%) before ATT and in only 1 (2.04%) woman after ATT (p < .001). Caseous nodules and encysted ascites were seen in 4 women (8%) before ATT, and in no women after ATT (p < .001); however, there was no change from before ATT to after ATT in the rate of pelvic adhesions (42% vs 42.5%) and perihepatic adhesions (56% vs 58%). Laparoscopic findings in fallopian tubes included hydrosalpinx (32%), pyosalpinx (4%), beaded tubes (12%), nonvisualization of tube (20%), and tubal blockage on the right side (56%), left side (50%), and both sides (38%) before ATT. Hydrosalpinx, beaded tubes, and nonvisualized tube were seen in 33.4%, 4.1%, and 20.8% cases, respectively, after ATT; however, free spill increased to 52% on the right side and 50% on left side after ATT. CONCLUSION: ATT improves laparoscopic findings in FGTB with infertility. However, advanced fibrotic lesions (eg, pelvic and perihepatic adhesions, bilateral blocked tubes) do not improve with ATT.

Hysteroscopic septal resection using unipolar resectoscope versus bipolar resectoscope: Prospective, randomized study.

AIM: To compare the operation and reproductive outcome of hysteroscopic septal resection using unipolar resectoscope verses bipolar resectoscope. METHODS: In this prospective randomized study, 70 women underwent hysteroscopic septal resection using either unipolar resectoscope or bipolar resectoscope. Intraoperative parameters (operation time, fluid deficit and complications) and pre- and postoperative serum sodium levels were compared between the two groups. A second-look hysteroscopy was performed after 6 weeks. All pregnancies occurring during the follow-up period were recorded. RESULTS: There was no statistically significant difference between the two groups in terms of operation parameters and second-look hysteroscopy findings. Six patients in the unipolar group were found to have hyponatremia in the postoperative period compared to none in the bipolar group (P = 0.025). Regarding reproductive outcome, the difference between the two groups was not significant. CONCLUSION: The use of bipolar resectoscope is associated with lesser risk of hyponatremia compared to unipolar resectoscope. Bipolar resectoscopy is a safe alternative to unipolar resectoscopy with similar reproductive outcome.

A repertoire of biomarkers helps in detection and assessment of therapeutic response in epithelial ovarian cancer.

In epithelial ovarian cancer (EOC), the cancer antigen 125 (CA-125) has been conventionally used to help in diagnosis and assessment of response to treatment. Currently, YKL-40 (Tyrosine-Lysine-Leucine-40) and circulating cell-free DNA are being evaluated for possession of similar ability. In this study, we aimed to assess the ability of a repertoire of potential biomarkers in detecting and assessing therapeutic response, in advanced EOC. Blood levels of CA-125, YKL-40, total cell-free DNA (CFDNA), cell-free nuclear DNA (CFnDNA), and cell-free mitochondrial DNA (CFmDNA) levels were measured in 100 untreated patients of advanced EOC from November 2009 to June 2011, and again on treatment completion from the 20 patients who appeared for follow-up analysis. Significantly, higher proportion of untreated patients had serum CA-125 >3 times upper limit of normal (ULN) (90.0%; P < 0.0001) and plasma YKL-40 >ULN (77.0%; P < 0.0001), both of which significantly decreased, Posttherapy. posttherapy, CFDNA (P < 0.0001), and CFnDNA (P < 0.0001) levels significantly decreased as compared to pretreatment levels. Positive and significant correlations existed between pretherapy CFDNA and CFnDNA [Spearman rho (ρ) = 1.000; P < 0.0001], and also with CFmDNA (ρ = 0.301; P = 0.002), separately between CFnDNA and CFmDNA (ρ = 0.303; P = 0.002), as well as between plasma YKL-40 and patient age (ρ = 0.353; (P < 0.0001). On treatment completion, CFDNA and CFnDNA levels showed positive and significant correlation (ρ = 1.000; P < 0.0001). Therefore serum CA-125 and plasma YKL-40 aid detection and assessment of therapeutic response, in advanced EOC. CFDNA and CFnDNA help in estimating extent of therapeutic response in advanced EOC.

Role of dehydroepiandrosterone in improving oocyte and embryo quality in IVF cycles.

The purpose of this study was to evaluate the role of dehydroepiandrosterone (DHEA) on the number and quality of oocytes and embryos in poor responders undergoing IVF cycles. A total of 50 patients with a history of poor ovarian response in the previous cycle(s) were enrolled in a prospective cohort study. They were treated with oral micronized DHEA 25mg three times a day for 4 months. Oocyte and embryo number and quality were recorded before and after treatment. The results were analysed using Student's paired t-test. After treatment with DHEA, a significant increase in number of mature follicles was seen in the post treatment period (⩽ 35 years P<0.001; ⩾ 36 years P = 0.002). There were significant increases in numbers of oocytes retrieved, fertilization rates and, consequently, the total number of embryos available. More embryos were vitrified among patients ⩽ 35 years (P<0.001) post treatment, and clinical pregnancy rate in this group was 26.7%. DHEA treatment resulted in a higher number of oocytes retrieved, oocytes fertilized, embryos overall and of grade-I embryos. It can help in increasing pregnancy rate in poor responders. This study was performed to evaluate the role of dehydroepiandrosterone (DHEA) treatment on the number and quality of oocytes and embryos in poor responders undergoing IVF cycles. Fifty patients with a history of poor ovarian response in the previous cycle(s) were enrolled in the study and a prospective cohort study was performed. Patients were prescribed oral micronized DHEA 25mg three times a day for 4 months. Oocytes and embryos in terms of both number and quality were measured before and after treatment. A significant increase in mean number of mature follicles was seen in the post-treatment group. There was a significant increase in the number of oocytes retrieved, fertilization rates and, consequently, in the total number of embryos available after treatment with DHEA. More embryos were vitrified post treatment and the overall pregnancy rate was 20%. DHEA resulted in a significant improvement in the numbers of oocytes retrieved, oocytes fertilized, embryos and grade-I embryos. DHEA can help improve pregnancy rate in poor responders with history of previous failed IVF cycles.

Serum one-carbon metabolites and risk of cervical cancer.

Most cases of cervical cancer are associated with human papilloma virus (HPV) infection of high risk types. In folate deficiency, heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) interferes with HPV16 viral capsid protein synthesis. We aimed to study the importance of 1-carbon metabolism in cervical carcinogenesis by examining serum vitamin B12 (cobalamin), homocysteine, folate levels, and the RNA and protein expression of HPV16 L1, L2, E6, E7, and to correlate them with hnRNP-E1 expression and HPV infection in normals, squamous intraepithelial lesions (SILs), and cervical cancer subjects. Serum cobalamin, folate, and homocysteine were estimated using kits, RNA by real time PCR and proteins by Western blotting. We observed that lower folate and vitamin B12 levels were associated with HPV infection. hnRNP-E1 progressively decreased from normals (100%) to SILs (75%) to cervical cancer (52.6%). The findings show that HPV16 E6 and E7 are overexpresed whereas HPV16 L1 and L2 are downregulated at mRNA and protein levels in cervical cancer as compared to normals and SILs. The results indicate that perhaps the reduced expression of hnRNP-E1 might be involved with the cervical cancer pathogenesis, with folate playing a role in the natural history of HPV infection.

Nucleic acid amplification tests (NAATs) for gonorrhoea diagnosis in women: experience of a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: Gonorrhoea is among the most frequent of the estimated bacterial sexually transmitted infections (STIs) and has significant health implications in women. The use of nucleic acid amplification tests (NAATs) has been shown to provide enhanced diagnosis of gonorrhoea in female patients. However, it is recommended that an on-going assessment of the test assays should be performed to check for any probable sequence variation occurring in the targeted region. In this study, an in-house PCR targeting opa-gene of Neisseria gonorrhoeae was used in conjunction with 16S ribosomal PCR to determine the presence of gonorrhoea in female patients attending the tertiary care hospitals. METHODS: Endocervical samples collected from 250 female patients with complaints of vaginal or cervical discharge or pain in lower abdomen were tested using opa and 16S ribosomal assay. The samples were also processed by conventional methods. RESULTS: Of the 250 female patients included in the study, only one was positive by conventional methods (microscopy and culture) whereas 17 patients were found to be positive based on PCR results. INTERPRETATION & CONCLUSIONS: The clinical sensitivity of conventional methods for the detection of N. gonorrhoeae in female patients was low. The gonococcal detection rates increased when molecular method was used giving 16 additional positives. Studies should be done to find out other gene targets that may be used in the screening assays to detect the presence of gonorrhoea.

Analgesic effectiveness of acetaminophen for primary cleft palate repair in young children: a randomized placebo controlled trial.

BACKGROUND: Clefting of the lip, palate, or both is a common congenital abnormality. Inadequate treatment for pain in children may result from concerns over opioid-related adverse effects. Providing adequate pain control with minimal adverse effects remains challenging in children. OBJECTIVES: To assess opioid-sparing effects of oral or intravenous acetaminophen following primary cleft palate repair in children. METHODS: Prospective randomized controlled trial in 45 healthy children, ages 5 months to 5 years, using standardized general anesthesia and lidocaine infiltration of the operative field. Patients were allocated to groups: intravenous acetaminophen/oral placebo (intravenous), oral acetaminophen/intravenous placebo (oral), or intravenous/oral placebo (control). Groups were compared for differences in opioid administration during the 24-h study period (morphine equivalents µg·kg(-1) ; 95% confidence interval). RESULTS: Intravenous acetaminophen decreased opioid requirement after surgery (P = 0.003). Patients in the intravenous group received less opioid (272.9; 202.9-342.8 µg·kg(-1) ) than control patients (454.2; 384.3-524.2 µg·kg(-1) ; P < 0.002). Opioid requirement in oral patients (376.5; 304.1-448.9 µg·kg(-1) ) was intermediate and not significantly different from either intravenous (P = 0.11) or control (P = 0.27). During the ward phase of care, intravenous had better analgesia than control (P = 0.002), and both intravenous and oral group patients received less opioid than control (P = 0.01). CONCLUSION: Intravenous acetaminophen given to young children undergoing primary cleft palate repair was associated with opioid-sparing effects compared to placebo. The fewer morphine doses during ward stay in both intravenous and oral may be important clinically in some settings.