Morning Sickness in early pregnancy linked to lower risk of miscarriages and still births.

Nausea and vomiting in early pregnancy affects 50-80% of pregnant women. Researchers have linked its etiology to imbalance in carbohydrate metabolism, rising hormonal levels in pregnancy, psychosomatic factors  evolutionary survival adaptation which protects pregnant mothers and their babies from food poisoning. 

 Few  observational studies in the past have documented that incidence of pregnancy loss is lower in patients who have morning sickness in first trimester.

A new study published in the in the journal JAMA Internal Medicine[1] found that women who suffer from nausea and vomiting in the first trimester have 50% less chance of miscarriage.

The study is a result of secondary data analysis of a Randomized Control Trial (RCT) examining Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial.[2] The EAGeR study is a multi-site, double-blinded randomized trial designed to assess the effects of low-dose aspirin on implantation and pregnancy outcome carried out by researchers at NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and other institutions.

The secondary analysis was limited to women who had a pregnancy confirmed by positive human chorionic gonadotropin (hCG) test, had a history of at least one pregnancy loss. A total of 797 study subjects was recruited. The women kept a daily diary for nausea and vomiting from week 2 to week 8 of pregnancy, and monthly thereafter.

Out of 797 pregnancies, 188 ended in loss (23.6%), and at the end of 8 weeks about 57.3 percent of the women reported experiencing nausea and 26.6 percent reported nausea with vomiting. 

In this cohort of women, it was seen that nausea alone or nausea with vomiting during pregnancy were associated with nearly 50%-75% reduction in the risk for pregnancy loss. When the analysis was done for peri-implantation pregnancy loss, the results were similar but they were not statistically significant.

Younger women (age <25 years) suffered much more with nausea and vomiting as compared to older women.

The association persisted even after accounting for confounding factors like maternal stress, alcohol intake, caffeine intake, smoking, fetal sex, multiple-fetal gestation, and karyotype.

Stefanie Hinkle, the lead author and a researcher at the national institute said "Our study evaluates symptoms from the earliest weeks of pregnancy, immediately after conception, and confirms that there is a protective association between nausea and vomiting and a lower risk of pregnancy loss.” But, was not sure whether the study results could be applied to primigravida.

She also went to stress that women with no nausea or vomiting should not be alarmed as a result of this study. "Every pregnancy is different and just because they don't have symptoms doesn't mean they're going to have a pregnancy loss," Hinkle said.[3]

The study was also followed by an accompanying editorial by Siripanth Nippita, MD, and Laura E. Dodge, ScD, MPH, from the Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center. They said "This study's contribution to the existing literature is valuable for several reasons. It builds on a prior cohort study by Sapra et al and similarly enrolled a large sample of women before conception."

They further quote “The widespread availability of sensitive urine hCG tests coupled with real-time electronic data capture using mobile phone apps or similar technology has the potential to improve data quality and eliminate recall bias. Given these methodologic advantages over previous investigations, we hope that such studies can further deepen our understanding of the underlying causes of [nausea and vomiting in pregnancy]."

The researchers also urged women with nausea and vomiting in pregnancy to seek medical consultation since it negatively affects the quality of life.

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[1] http://archinte.jamanetwork.com/article.aspx?articleid=2553283

[2] http://grantome.com/grant/NIH/ZIA-HD008795-08

[3] Stefanie N. Hinkle, Sunni L. Mumford, Katherine L. Grantz, Robert M. Silver, Emily M. Mitchell, Lindsey A. Sjaarda, Rose G. Radin, Neil J. Perkins, Noya Galai, Enrique F. Schisterman. Association of Nausea and Vomiting During Pregnancy With Pregnancy Loss. JAMA Internal Medicine, 2016; DOI: 10.1001/jamainternmed.2016.5641

Guidelines revised for preventing thromboembolism in pregnancy.

Obstetric Venous thromboembolism (VTE) is a leading cause for maternal morbidity and mortality. Venous thromboembolism encompasses deep vein thrombosis(DVT) and pulmonary embolism (PE) complicates 0.5 to 3.0 per 1,000 pregnancies.[1] PE is the seventh leading cause of maternal mortality and contributes to 9% of maternal deaths.[2]

Maternal deaths due to VTE are preventable by forming and implementing comprehensive guidelines for prophylaxis of thromboembolism. But, presently sufficient clinical trial data remains unavailable to formulate VTE prophylaxis guidelines in pregnancy.

In US only women who are at high risk for VTE receive pharmacologic prophylaxis, thereby increasing the rate of obstetric VTE in the last decade.

On the contrary, RCOG guidelines in U.K recommend screening and assessment of antepartum and postpartum women for at risk for VTE. Due to regular assessment many women receive pharmacologic thromboprophylaxis, bringing down the rates of VTE since the release of the guidelines.

Observational data support risk-factor-based prophylaxis in bringing down the incidence of VTE, hence the National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care developed safety bundle. Safety bundle supports routine risk evaluation for obstetric patients with pharmacological and mechanical thromboprophylaxis when needed. [3] It outlines simple practices that can be implemented in every maternal units, adapting according to the healthcare resources available in each community.

The article was published in October issue of Obstetrics and Gynecology journal.[4] The bundle is grouped into 4 domains: Readiness, Recognition, Response, and Reporting and Systems Learning. 

Readiness: Every Unit should use standard VTE risk assessment tool during prenatal outpatient visits, antepartum admissions to hospital, post labor and post cesarean stay in hospitals and 6 weeks postpartum.

Recognition and Response: Once the risk assessment is done, physicians should use patients Caprini[5] or Padua score[6] to identify those patients who will need thromboprophylaxis according to clinical situation and risk score. The thromboprophylaxis guidelines are as advocated by ACOG, American College of Chest Physicians and RCOG.

• Antepartum outpatient prophylaxis: women with a history of multiple VTE or thrombophilia episodes low-molecular-weight (LMW) heparin or unfractionated heparin (UFH) is recommended.
• Antepartum Inpatients for more than 3 days: Women who are not at risk for bleeding or imminent childbirth, prophylaxis with daily LMW heparin or twice-daily UFH is advocated.
• Women with a history of VTE who are undergoing a trial of vaginal birth are given intrapartum mechanical thromboprophylaxis using pneumatic compression devices while in bed. After the delivery, LMW heparin or UFH can be for those at high risk for VTE based on RCOG criteria or a Padua score of 4 or greater.
• Those women undergoing an operative delivery are prescribed mechanical thromboprophylaxis using pneumatic compression. Once the surgery is over, they can also be given LMW heparin or UFH, based on RCOG criteria or modified Caprini scores.
• RCOG criteria also advocates that all women who are undergoing operative delivery may be routinely prescribed LMW heparin or UFH due to complications with mechanical prophylaxis.
• Women with repeated history of VTE, high-risk thrombophilia, or VTE with acquired thrombophilia can be put on extended 6-week treatment-dose of LMW heparin or UFH postpartum.

Reporting and Systems Learning: All centers should meticulously keep records of patients receiving prophylaxis for VTE, adverse reactions and complications.  Routine audits should be performed to check whether physicians are evaluating, assessing the risk factors for VTE and planning the treatment accordingly.

However, in an accompanying editorial Baha M. Sibai, MD, from the University of Texas Medical School at Houston, and Dwight J. Rouse, MD, MSPH, associate editor for Obstetrics & Gynecology, have expressed concern that the widespread use pharmacological prophylaxis may do more harm than good. 

The authors are specially concerned with 3 days’ prophylaxis for antepartum hospitalized patients and women at high risk for VTE and have undergone vaginal birth.

They were especially worried about following the RCOG criteria of pharmacological prophylaxis after cesarean delivery, which would apply to more than half of the C.S. patients in the US. 

According to the editorial analysis” approximately 1 million women would require pharmacologic prophylaxis to prevent even one maternal death from cesarean delivery–associated pulmonary embolism."

Nevertheless, they advocate the use of mechanical prophylaxis in all obstetrics units’ post-cesarean and building a database of huge obstetric patients in whom the mechanical method was used. In the future, this large data base created can be used to assess the pros and cons of using pharmacological prophylaxis in obstetrics patients.

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[1] Snow V, Qaseem A, Barry P, et al., for the American College of Physicians, American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism. Management of venous thrombo-embolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146(3):204–210....

[2] The Confidential Enquiry into Maternal and Child Health (CEMACH). Saving mothers’ lives: reviewing maternal deaths to make motherhood safer — 2003–2005: the seventh report on confidential enquiries into maternal deaths in the United Kingdom. London: CEMACH, 2007

[3] http://www.safehealthcareforeverywoman.org/secure/vte-prevention-patient-safety-bundle.php

[4] http://journals.lww.com/greenjournal/Citation/2016/10000/National_Partnership_for_Maternal_Safety_.3.aspx

[5] http://www.wikidoc.org/index.php/Caprini_risk_assessment_model

[6] http://www.mdcalc.com/padua-prediction-score-for-risk-of-vte/

Novel Investigational antibiotic for Gonorrhea holds a promise for future with 100% cure rate.

Gonorrhea is one of the most common STD in US. Recently public health officials have identified cluster of gonorrhea cases in Hawaii that show decreasing susceptibility to ceftriaxone and high level of resistance to azithromycin. [1] 

Currently a combination of ceftriaxone and azithromycin is the last available option for treating gonorrhea and investigators believe that they will run out of this option in near future. Left untreated, gonorrhea can lead to serious health problems including infertility, pelvic inflammatory disease and life-threatening ectopic pregnancy in women.

• One third of the new gonorrhea infection are resistant to at least 1 drug.
• It is the most common communicable disease in the US, with an estimated 820,000 new infections each year.
• We are only left with 1 treatment option for gonorrhea out of 5 reported by CDC in 2006 due to development of resistance by the bacteria.

Hence, researchers have renewed interest in development of new drug for gonorrhea. At the 2016 STD Prevention Conference, researchers from Louisiana State University presented results of phase 2 clinical trials of experimental oral antibiotic that was safe and effective in treating uncomplicated gonorrhea. Unlike any other marketed antibiotic, the new drug dubbed as ETX0914 is a novel spiropyrimidinetrione, that acts by inhibiting deoxyribonucleic acid biosynthesis by accumulation of double strand cleavages. [3]

In a small clinical trial, a total of 179 participants (167 men and 12 women) were randomized approximately 70:70:40 to receive either 2000mg or 3000mg ETX0914 orally or 500mg ceftriaxone in a single intramuscular injection.

Patients were followed up for safety, microbiological and clinical cure rates. The drug was well tolerated with only mild gastrointestinal side effects.

All patients receiving 3g ETX0914 (47/47) and 98 percent of patients in the 2g group (48/49) were cured. 

The trials lead investigator Stephanie N. Taylor, M.D., professor of medicine and microbiology at Louisiana State University Health Sciences Center said “We are very pleased with these results and look forward to seeing ETX0914 advance through additional clinical studies.”

The combination therapy of azithromycin and ceftriaxone recommended by CDC is still effective, but “ will eventually fail” says  Jonathan Mermin, MD, director of the CDC's center for HIV/AIDS, viral hepatitis, STD, and TB prevention quotes "In the battle between humans and pathogens," he said, "gonorrhea is a formidable opponent."

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[1] https://www.cdc.gov/nchhstp/newsroom/2016/2016-std-prevention-conference-press-release.html

[2] https://www.cdc.gov/stdconference/2016/highlights/arg.html

[3] https://cdc.confex.com/cdc/std2016/webprogram/Paper37739.html