Maternal clinical risk factors for increased rate of post cesarean infection identified.

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Preincisional extended antibiotic prophylaxis does not prevent occurrence of maternal infections that significantly contributes to increased maternal morbidity in cesarean sections.

Maternal BMI, rupture of membranes to delivery interval, race and duration of surgery are important contributing factors towards maternal infection even after prophylactic antibiotics were given according to a study published online ahead of print in Journal of obstetrics and gynecology.

This was a secondary analysis Cesarean Section Optimal Antibiotic Prophylaxis trial (C/SOAP),that concluded that pairing Azithromycin with standard pre-incisional prophylaxis reduced the surgical site infection by nearly 50%.  Dr. Alan Tita presented the paper  at the 36^th Annual Pregnancy Meeting 2016 sponsored by the Society for Maternal-Fetal Medicine.

The secondary analysis of the data was done in an effort to further identify maternal clinical risk factors that can further reduce the risk of maternal infections.

The primary outcome studied was maternal infection and consists of  a composite of endometritis, wound infection (superficial or deep), or other infections occurring up to 6 weeks postpartum.

Data from all 2013 patients in the primary study was included in the secondary analysis.

After controlling for Azithromycin: maternal age, duration of ROM, duration of surgery, vertical or non-transverse skin incision, staple skin closure, BMI and labor induction significantly influenced the incidence of maternal morbidity.

After parsimonious regression model, in which those variables that were statistically non-significant were removed from the analysis, showed that black race, duration of rupture of membranes more than 6 hours and duration of surgery more than 49 minutes were significantly associated with increased maternal infection.

If duration of rupture of membrane exceeds 6 hours than the rate of maternal infection increases by 1.9 to 3.4-fold.

In addition, in unadjusted analysis patients with BMI more than 30 had 2.5 times higher risk of infection as compared to those with BMI< 25 in whom the risk of infection  was minimal.

The researchers advocate need of additional studies in patients with these risk factors to formulate guidelines for further reduction in infectious morbidity.

One third of postmenopausal breast cancers are preventable because of modifiable risk factors.

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Modifiable risk factors account for a large proportions of breast cancer cases and Identification of this factors is the key to bring down the incidence of postmenopausal breast cancer says the result of a study published in December issue of American Journal of Epidemiology. [1]

This study mainly focused on those population based risk factors that are modifiable at menopause.

Incidence of breast cancer vary across the globe and geographical variation in prevalence rate suggest that modifiable risk factors play a role in its causation.

www.nationalbreastcancer.org

Out of multiple population attributable risk factors identified some are non-modifiable like height, BMI, family H/O breast cancer, prior benign breast lump and reproductive factors such as parity, age at first birth and reproductive life span.

This study analyzed the data from Nurses Health study that spanned over 20 years from 1980-2010.   It was seen that 8,421 cases of postmenopausal breast cancer developed out of 121,700 women in the study.[2]

When all the risk factors were analyzed and controlled for age, the PAR% for developing breast cancer was 70%. Population Attributable Risk (or Population Attributable Fraction) indicates the number (or proportion) of cases that would not occur in a population if the factor were eliminated.

That means 70% of cases of breast cancer developed in patients who had known risk factors for the disease other than age. Majority of these attributable risk factors were non-modifiable but nearly one third were modifiable. Greatest risk was seen in patients who gained a substantial weight at age 18.

CDC.gov

The modifiable Population Attributable Risk(PAR) factors identified in the study are weight change since age 18 years, alcohol consumption, physical activity level, breastfeeding, and menopausal hormone therapy use.

Changes in these 5 modifiable risk factors could reduce the rate by 34%.

Variations in the non-modifiable risk factors among different geographical locations explain the large variation in incidence of the disease across international borders.

 To conclude, keeping the weight gain to minimum, no drinking, high physical activity, breast feeding and no hormone replacement therapy was responsible for population attributable risk percentages (PAR%) of 34%, it was moderately higher for ER+ (PAR% = 39.7%) than ER–breast cancers (PAR% = 27.9%).

Breast cancer is a major cause of morbidity and mortality worldwide and it is most common cancer in women in US. Some statistics about breast cancer in US by breastcancer.org are:

• About 1 in 8 U.S. women (about 12%) will develop invasive breast cancer over the course of her lifetime and more than 77% occur in women over the age of 50 years.
• About 85% of breast cancers occur in women who have no family history of breast cancer. 
• In 2017, an estimated 255,180 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S., along with 63,410 new cases of non-invasive (in situ) breast cancer.
• About 40,610 women will die from breast cancer in 2017.

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[1] https://academic.oup.com/aje/article-abstract/184/12/884/2645430/Population-Attributable-Risk-of-Modifiable-and?redirectedFrom=fulltext

[2] http://www.nurseshealthstudy.org/

Vitamin D and Human Reproduction—Evolving perspectives

We are all well versed with the role of Vitamin D in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. Its deficiency is linked to many chronic diseases of the cardiovascular and metabolic systems.

Evidence from animal and human studies suggests that vitamin D plays a very important role in human fertility and neonatal development. This steroid hormone has Vitamin D receptors (VDR) at multiple sites in the body including ovary, particularly the granulosa cells, endometrium and placenta.

It plays a very important role in ovarian steroidogenesis. [1] It deficiency contribute to development of insulin resistance and impaired glucose metabolism in patients with Polycystic Ovary Syndrome (PCOS). Therapeutic efficacy of supplementation with Vitamin D to improve insulin resistance, bring about ovulation and regularize menstruation in PCOs patients have been documented.[2] [3]

Observations also shows that lower 25(OH)D levels put women at higher risk of developing uterine fibroids, both in black and white ethnicities. In these women, the growth and size of the fibroid is also directly related to decreased levels of Vitamin D. Animal studies and human in vitro studies have shown the beneficial effect Vitamin D supplementation in inhibition of development and/or growth of uterine fibroids.[4] [5]

A recent study by Harris HR et al demonstrated that women within the highest quintile of Vitamin D blood values have one fourth the risk of developing endometriosis as compared to those in lowest quintile.[6]

It also plays a role in Body Mass Index (BMI) as per a recent meta-analysis, every 10% increase in BMI leads to 4% decrees in Vitamin D concentration.[7]

It’s role in male reproductive physiology is well documented by the fact that it’s level directly correlate with sperm motility and morphology.

As per Hill’s criteria a causal relationship between Vitamin D deficiency and negative outcome in IVF is explained but further research into knowing the magnitude of association is needed.[8]

A systemic review and meta-analysis by Lerchbaum E and Obermayer-Pietsch B published in Eur J Endocrinol May 1, 2012 concludes that Vitamin D plays an important role in Human reproduction and advocates the need of further research in therapeutic benefits of Vitamin D supplementation in such patients.  

Another review by Vanni et al published in the Reproductive Biology and Endocrinology, 2014 emphasizes the importance of supplementation of Vitamin D in IVF settings because consisting evidence documenting the increase incidence of gestational diabetes, IUGR, pre-eclampsia and preterm births in patients deficient in Vitamin D.[9]

The authors opine that although drastic improvements in reproductive failure may not be achieved solely by supplementing Vitamin D, but its addition to any fertility regimen is cheap, effective and without any side effects. It is easily correctable by simple oral supplementation.

Dosage up to 4000 IU is safe, without any side effects and effectively improve maternal vitamin D status. [10]

Results of double blind randomized trial entitled “Vitamin D during IVF” is still awaited.[11]

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[1]Anagnostis P, Karras S, Goulis DG: Vitamin D in human reproduction: a narrative review. Int J Clin Pract. 2013, 67 (3): 225-235

[2] Selimoglu H, Duran C, Kiyici S, Ersoy C, Guclu M, Ozkaya G, Tuncel E, Erturk E, Imamoglu S: The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome. J Endocrinol Invest. 2010, 33 (4): 234-238.

[3] Wehr E, Pieber TR, Obermayer-Pietsch B: Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study. J Endocrinol Invest. 2011, 34 (10): 757-63.

[4] Bläuer M, Rovio PH, Ylikomi T, Heinonen PK: Vitamin D inhibits myometrial and leiomyoma cell proliferation in vitro. Fertil Steril. 2009, 91 (5): 1919-1925.

[5] Halder SK, Osteen KG, Al-Hendy A: Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and −9 in human uterine fibroid cells. Hum Reprod. 2013, 28 (9): 2407-2416.

[6]  Harris HR, Chavarro JE, Malspeis S, Willett WC, Missmer SA: Dairy-food, calcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort study. Am J Epidemiol. 2013, 177 (5): 420-430.

[7] Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Kiraki LT, Cooper JD, Dastani Z, Li R, Houston DK, Wood AR, Michaëlsson K, Vandenput L, Zgaga L, Yerges-Armstrong LM, McCarthy MI, Dupuis J, Kaakinen M, Kleber ME, Jameson K, Arden N, Raitakari O, Viikari J, Lohman KK, Ferrucci L, Melhus H, Ingelsson E, Byberg L, Lind L, Lorentzon M, et al: Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013, 10 (2): e1001383-

[8] Hill AB: The environment and disease: association or causation?. Proc R Soc Med. 1965, 58: 295-300.

[9] Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O’Beirne M, Rabi DM: Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ. 2013, 26 (346): f1169-

[10] Wagner CL, McNeil R, Johnson DD, Husley TC, Ebeling M, Robinson C, Hamilton SA, Hollis BW: Health characteristics and outcomes of two randomized vitamin D supplementation trials during pregnancy: a combined analysis. J Steroid Biochem Mol Biol. 2013, 136: 313-320.

[11] https://clinicaltrials.gov/ct2/show/NCT01019785

The New Puberty

The New Puberty

The Book" The new puberty"

This article is based on TEDMED talk 2015 in Palm Springs, California by Pediatric endocrinologist Louise Greenspan and her groundbreaking book, -“The New Puberty: How To Navigate Early Development in Today’s Girls”, along with coauthor Julianna Deardorff, a Berkeley professor of Maternal and Child Health and adolescent psychologist.

Just a generation ago, fewer than 5 percent of girls started puberty before the age of 8, today girls are entering puberty at increasingly younger ages with 10% of girls now showing the first signs of puberty before age 8.

Early puberty can lead to eating disorders, depression, substance abuse, early sexual activity and, later in life, breast cancer.

According to Dr. Greenspan, two important culprits responsible are obesity and family stress.

"We used to say that breast development and pubic hair should not start before age 8. What we know now is that 15% of girls at age 7 are showing breast development," Dr Greenspan reported.

According to Biro.F.M  et al in Pediatrics 2013;132:1019-1027 Girls from racial and ethnic groups with the highest rates of obesity are most at risk for early puberty. In that study, black girls showed breast budding at an average age of 8.75 years, Hispanic girls at an average age of 9.25 years, and white and Asian girls at an average age of 9.75 years.

Higher BMI was the strongest predictor of earlier age at breast stage 2 in this study

The relationship between higher BMI and earlier onset of puberty in girls has been noted previously; in 2 large cross-sectional studies, Pediatric Research in Office Settings (PROS) and the National Health and Nutrition Examination Survey (NHANES) III, earlier maturation occurred in those girls with greater BMI and in those with BMI ≥85th percentile.

Body fat makes estrogens, which are the same kind of hormone that are normally released from the ovaries during puberty. When there is more body fat, there are higher levels of estrogen, which leads to breast budding.

In USA the rate of obesity in children aged 6 to 11 years of age increased from 7% in 1980 to nearly 18% in 2012, according to a report from the Centers for Disease Control and Prevention.

And during the same period, the rate of adolescents 12 to 19 years of age who were obese increased from 5% to nearly 21%.

The trend is not just seen in the U.S., it's seen in multiple countries, probably more so countries closer to the equator than countries in the northern latitudes. But major factor is likely to be, certainly in the developing countries, a switch from a more traditional diet to a more Western diet, which results in greater, perhaps better nutrition or perhaps over-nutrition, and that's certainly a factor.

Stress is the second important factor in causing early puberty; other risk factors are early sexual abuse and toxic levels of family arguments and neighborhood violence.

Dr Greenspan says that “Most notably, a girl who grows up without her biological father is twice as likely to get her period before age 12 as a girl who lives with her biological father.”

She does not refute the endocrine-disrupting chemicals commonly found in plastics and pesticides for early puberty, but it is almost impossible to eliminate endocrine-disrupting chemicals from our environment, and there is no single smoking gun, she explained.

These chemicals can mimic hormones in the body, and some mimic hormones that are important regulators of puberty, particularly estrogen. However, more research is needed on humans.

She noted that "a much more effective public health intervention would be to try to tame the obesity epidemic and put some greater social infrastructure in place to buffer children from the stresses of poverty."

The authors offer highly practical strategies that can help prevent and manage early puberty including limiting exposure to certain ingredients in personal care and household products, which foods to eat and which to avoid, and ways to improve a child’s sleep routine to promote healthy biology.

Moreover, the authors—both mothers of young girls—offer parents, teachers, coaches, and caretakers guidance to initiate and continue the conversation about puberty in an age-appropriate way to support girls as they navigate this complex stage of their lives.

References:

http://thedianerehmshow.org/shows/2015-05-06/whats-behind-early-puberty-in-girls

http://www.jpagonline.org/article/S1083-3188%2812%2900092-7/abstract?cc=y

http://pediatrics.aappublications.org/content/132/6/1019.long

http://www.nytimes.com/2015/02/05/opinion/what-causes-girls-to-enter-puberty-early.html?_r=0

Rosenfield RL, Lipton RB, Drum ML. Thelarche, Pubarche, and Menarche Attainment in Children With Normal and Elevated Body Mass Index. PEDIATRICS 2009;123(1): 84–88

http://pediatrics.aappublications.org/content/132/6/1019.long#xref-ref-4-1