At least one year is the ideal pregnancy spacing time for the health of mother and baby

  

One to one and a half year is the ideal spacing time between pregnancies according to researchers from the University of British Columbia (B.C.) and the Harvard T.H. Chan School of Public Health.

The study found an increased risk of premature births, maternal morbidity and mortality, and adverse neonatal outcome following an interpregnancy interval of fewer than 12 months in women of all ages. However, women who were 35 or more were at increased risks of maternal mortality or severe morbidity, while women aged 20 to 34 years were at increased risk of preterm labor and adverse fetal and infant outcomes.

In this large cohort study published online October 29 in JAMA Internal Medicine, the researchers looked at data from 148,544 pregnancies in B.C. to examine the relationship between interpregnancy interval and adverse pregnancy. The data was gathered from billing codes, hospitalization data, birth records, prescription data for infertility information, and census records for a period of 10 years (2004 to 2014).

The study is the most extensive and in-depth evaluation of the relationship between pregnancy spacing and maternal age. Currently, it is unknown whether older women face the same risk as younger women because of a shorter interpregnancy interval.

Women aged 35 and more who conceived within six months of a previous birth, faced 1.2 percent risk (12 cases per 1,000 pregnancies) of maternal mortality or severe morbidity (mechanical ventilation, blood transfusion >3 U, intensive care unit admission, and organ failure). Keeping an interpregnancy interval of 18 months, however, reduced the risk to 0.5 percent (five cases per 1,000 pregnancies).

For younger women, who conceived within six months of last childbirth, the researchers found an 8.5 percent risk (85 cases per 1,000 pregnancies) of spontaneous preterm birth, but the risk dropped to 3.7 percent (37 cases per 1,000 pregnancies) if the women waited 18 months before the next conception. 

Among older women, the risk of spontaneous preterm labor was about six percent (60 cases per 1,000 pregnancies) at the six-month interval, compared to 3.4 percent (34 cases per 1,000 pregnancies) at the 18-month interval.

“Our study found increased risks to both mother and infant when pregnancies are closely spaced, including for women older than 35,” said the study’s lead author Laura Schummers in a University of British Columbia news release. Dr. Schummers is a postdoctoral fellow in the UBC department of family practice who carried out the study as part of her dissertation at the Harvard T.H. Chan School of Public Health. “The findings for older women are particularly important, as older women tend to more closely space their pregnancies and often do so intentionally,” she further added. 

Senior author Dr. Wendy Norman, associate professor in the UBC department of family practice, said these findings of a shorter optimal interval are encouraging for women over 35 who are planning their families.

“Older mothers for the first time have excellent evidence to guide the spacing of their children,” said Norman. “Achieving that optimal one-year interval should be doable for many women and is clearly worthwhile to reduce complication risks.”

JAMA Internal Medicine Full Text

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Vaginal Progesterone supplementation decreases preterm births, neonatal morbidity and mortality in women with twin gestation and short cervix: an updated meta-analysis of individual patient data

Administration of vaginal progesterone to asymptomatic women with a twin gestation and a sonographic short cervix (cervical length ≤ 25 mm) in the mid-trimester reduces the risk of preterm birth occurring at < 30 to < 35 gestational weeks, neonatal mortality and some measures of neonatal morbidity, without any demonstrable deleterious effects on childhood neurodevelopment.

The article was published online in Ultrasound in Obstetrics and Gynecology, the official journal of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG).

The meta-analysis included the results of 6 studies, encompassing 303 women pregnant with twins, all of whom had a cervical length of 25 mm or less in the midtrimester. Of these, 159 women received vaginal progesterone and 144 received a placebo or no treatment. Women who received vaginal progesterone were 31 percent less likely to deliver before 33 weeks of pregnancy (31 percent for those receiving vaginal progesterone, compared to 43 percent for those who did not). Vaginal progesterone also reduced the rate of preterm delivery before 32 weeks and 34 weeks. All results were statistically significant.

The risk of preterm birth < 33 weeks was reduced by 31% and neonatal death by 47% and also reduced the rate of respiratory distress syndrome (RDS), birth weight < 1500 g and use of mechanical ventilation.

No significant difference in the risk of neurodevelopmental disability at 4–5 years of age between children exposed prenatally to vaginal progesterone and those exposed to placebo.

“The findings represent persuasive evidence that treatment with vaginal progesterone in women with a short cervix and a twin gestation reduces the frequency of preterm birth, neonatal complications such as respiratory distress syndrome, and importantly, neonatal death,” said the study’s first author, Roberto Romero, M.D., Chief of the Perinatology Research Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD/NIH). Dr. Romero emphasized that individual patient data meta-analyses represent the “gold standard” in the hierarchy of scientific evidence to answer clinical questions.

Access the full article.

Access the press release.

The accompanying videoclip by the  ISUOG summarizes the importance of research. 

Air pollution identified as a possible risk factor for nearly 3 million preterm births every year.

Air pollution 

Outdoor air pollution has been identified as a possible risk factor for preterm births across the globe according to a study published in Journal of Environment International online February 10, 2017.[1] 

The 2010 study estimated that 2.7–3.4 million preterm births may be prevented if PM_2.5 exposure is brought down.

It is estimated that 14·9 million babies were born preterm worldwide in 2010.

There exists a wide disparity between Preterm Births(PTBs) rates across the globe, European countries have the lowest rate at 4-5% vs. countries in Africa and South Asia with rates as high as 15–18%.

In South Asia, about 1 million   PM_2.5 associated PTBs happened in India, followed by China which contributed another 500,000.

                                       

A pregnant woman in India or China will likely be exposed to 10 times more pollution as compared to a woman in Canada or UK.

It is estimated that in 2010, out of 135 million livebirths globally 14.9 million babies (11.1%) were preterm, including both spontaneous and iatrogenic births. [2]

Exposure of mother to fine particulate matter(PM) has been identified as one of the many risk factors for PTBs as well low birth weight babies. The fine PM finds its way into blood stream through lungs and causes pulmonary and placental inflammation, coagulopathies, endothelial dysfunction and hematological responses.

Fine particles are produced from all types of combustion, including motor vehicles, power plants, solid cooking fuels, residential wood burning, forest fires, agricultural burning, and some industrial processes.

Desert dust also contributes to Particulate Matter ( PM) and in Sub Saharan Africa, Middle East and North Africa it is the major exposure. 

"Air pollution may not just harm people who are breathing the air directly - it may also seriously affect a baby in its mother's womb," said Chris Malley, lead author of the study which is based on data for 2010.

The study further demonstrated that majority of the PM_2.5 associated preterm birth could be prevented by implementing strict emission control strategies in these regions except in in Sub Saharan Africa, Middle East and North Africa where nothing much can be done to change the geography of the area.

Johan Kuylenstierna, co-author of the study, and SEI's policy director said "In a city, maybe only half the pollution comes from sources within the city itself - the rest will be transported there by the wind from other regions or even other countries."

Nevertheless, the study demonstrated that reduction of maternal PM_2.5 exposure through emission reduction strategies could bring down the global preterm rate, limit in utero exposure to PM_2.5 bringing down postnatal and long term neonatal morbidity.

Exposure to PM_2.5 is also responsible for 9–14% of total preterm births globally out of the total risk percentage. It should also be targeted along with other risk factors to reduce the incidence of preterm birth.

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[1] http://www.sciencedirect.com/science/article/pii/S0160412016305992

[2] http://www.sciencedirect.com/science/article/pii/S0140673612608204

17α-hydroxyprogesterone caproate plus cerclage have cumulative effect in preventing recurrent preterm birth and improving perinatal outcome.

Clinical Pearls:    

·         Women receiving transvaginal cerclage plus 17α-hydroxyprogesterone caproate had a 69% relative reduction in delivery at less than 24 weeks of gestation when compared with women receiving cerclage alone. 

·         These women also delivered babies that were heavier (2,547±1,009 g) as compared to women with only cerclage (2,326±1,250 g). (P=.03)

·         They also had fewer neonates with with 5-minute Apgar score less than 7,10% in the cerclage plus 17α-hydroxyprogesterone caproate cohort compared with 20% in the control cohort (P=.04).

·         There was no significant difference in delivery at less than 28 and less than 37 weeks of gestation, neonatal complications and admission to NICU between the two cohorts. 

·         The pilot study results indicate that the two therapies, 17α-hydroxyprogesterone caproate and cerclage, appear to be cumulative in their benefit.

Preterm birth is a major cause of neonatal morbidity and mortality with most preterm-related deaths occurring among babies who were born very preterm (before 32 weeks). Preterm birth is also a leading cause of long-term neurological disabilities in children.[1]

As per WHO statistics every year nearly 15 million babies are born preterm (1 in 10 babies) and it was responsible for nearly 1 million deaths in 2013.

In India, 3,341,000 babies are born preterm each year and 361,600 children under five die due to direct preterm complications.[2] More than 90% of babies born before 28 weeks of gestation in developing countries succumb within first few days of birth while in developed countries less than 10% babies of the same gestation die.[3]

Beside other risk factors, a history of prior preterm birth is the single most important risk factor for subsequent preterm birth.

A meta-analysis by Berghella V et al published in obstetrics and gynecology journal compared the outcome in singleton gestations with prior preterm birth that were managed either by cervical length screening with cerclage for short cervical length or history-indicated cerclage. The study concluded that cerclage is not indicated in every woman with previous history of preterm birth but reserved for the minority of women who develop a short cervical length.[4]

ACOG February 2014 Practice Bulletin reviews the guidelines for cervical cerclage in women with a history of preterm birth based on history, physical examination, and ultrasonographic findings.[5]

The second modality of treatment for women with a prior preterm birth is 17α-hydroxyprogesterone caproate. A study by Meis  PJ et al showed that weekly  injection of 250 mg 17 alpha-hydroxyprogesterone caproate reduced the risk of preterm birth before 37 weeks by nearly 34%.[6]

The additive effects of cerclage plus 17 alpha-hydroxyprogesterone caproate versus only cerclage in patients with a prior spontaneous preterm delivery has not been studied.  

The recent study published in obstetrics and gynecology November 2016 issue compared the prolongation of pregnancy and perinatal outcome in   among women with a prior preterm birth who received cerclage compared with cerclage plus 17α-hydroxyprogesterone caproate.

This retrospective cohort study recruited patients with vaginal cerclage and prior history of preterm birth between 16-36 weeks of gestation were identified over a course of 10-year period from July 2002 to May 2012.

A total of 411 women with cerclage were identified out of whom 260 met the inclusion criteria.  Of these, the control arm of 171 women continued the pregnancy with cerclage alone while 89 women in the study arm received 250 mg of 17α-hydroxyprogesterone caproate injections weekly along with the cerclage. In 46 women with a history based cerclage the injections were started prior to surgery and in 43 patients they were started after the procedure.

The primary outcome was delivery before 24 weeks while the secondary outcomes were delivery at less than 28 and less than 37 weeks of gestation as well as preterm prelabor rupture of membranes (PROM), delivery mode, neonatal intensive care unit admission, 5-minute Apgar score less than 7, necrotizing enterocolitis, grade 3 or 4 intraventricular hemorrhage, and birth weight.

The two groups were identical in terms of maternal demographics and gestational age of receiving cerclage.

It was seen that women receiving transvaginal cerclage plus 17α-hydroxyprogesterone caproate had a 69% relative reduction in delivery at less than 24 weeks of gestation when compared with women receiving cerclage alone. 

These women also delivered babies that were heavier (2,547±1,009 g) as compared to women with only cerclage (2,326±1,250 g). (P=.03)

They also had fewer neonates with with 5-minute Apgar score less than 7. 10% in the cerclage plus 17α-hydroxyprogesterone caproate cohort compared with 20% in the control cohort (P=.04).

There was no significant difference in delivery at less than 28 and less than 37 weeks of gestation between the two cohorts. 

 Both the cohorts also have similar mode of delivery, neonatal intensive care unit admission, intraventricular hemorrhage (grade 3 or 4), or necrotizing enterocolitis.

A secondary analysis studies the relationship between examination and ultrasound indicated cerclage with the additive effect of 17α-hydroxyprogesterone caproate as compared to history indicated cerclage. There was a 91% and 89% reduction in delivery at less than 24 and less than 28 weeks of gestation, respectively when progesterone was continued.

The study has multiple strengths and limitations. The investigators understand that the study had a small sample size and limitations of adjusting for several variables. They also caution the readers to interpret the results of the study carefully as more large, adequately powered multicenter prospective trial studies are needed before a recommendation can be made.

The pilot study results indicate that the two therapies, 17α-hydroxyprogesterone caproate and cerclage, appear to be cumulative in their benefit.

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[1]http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm

[2] http://www.everypreemie.org/wp-content/uploads/2016/02/India-revJan2016.pdf

[3] http://www.who.int/mediacentre/factsheets/fs363/en/

[4] http://journals.lww.com/greenjournal/Abstract/2011/07000/Cervical_Length_Screening_With.20.aspx

[5] Cerclage for the management of cervical insufficiency. Practice Bulletin No. 142. American College of Obstetricians and Gynecologists. Obstet Gynecol 2014;123:372–9.

[6] https://www.ncbi.nlm.nih.gov/pubmed/12802023

History of uterine evacuation is an independent risk factor for preterm birth: a systematic review and meta-analysis.

Preterm birth(PTB) is the birth of an infant before 37 weeks of pregnancy, according to WHO statistics an estimated 15 million babies born preterm out of whom 1 million succumb. PTB is also responsible for long term neurological complications in children like cerebral palsy, learning disabilities and visual and hearing problems.

The current global preterm birth rate is 5% to 18% and statistic shows a steady increase recently.More than 60% of preterm births occur in Africa and South Asia, India topping the list with 3 519 100 PTBs

Three forth of these births could be prevented, saving lives and money across the globe.

CDC data quotes that in the year 2014, every 1 in 10 infants was born preterm in US. For physician across the globe, PTB remains a challenge as the factors leading to preterm births are numerous, complex and not well understood. Among various contributing factors prior uterine surgery, especially those performed on cervix (induced termination of pregnancy (I-TOP) or spontaneous abortion (SAB)) has been implicated in its causation. Studies till now have shown mixed results.

The current research published in May 2016 issue of American Journal of Obstetrics and Gynecology evaluated the risk of PTB in women with a history of uterine evacuation for I-TOP or SAB.

For the data source electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, and Sciencedirect) were searched from their inception until January 2015. Women with prior history of uterine evacuation for either I-TOP or SAB, compared with a control group without a history of uterine evacuation were included in the study.

Total 36 case control studies involving 1,047,683 women (31 studies for I-TOP, 5 studies for SAB) met the inclusion criteria and were included in the analysis.

The primary outcome was relationship between prior evacuation and subsequent preterm births while the secondary outcome studied were low birthweight (LBW) and small for gestational age (SGA). 

Relationship between PTB and prior H/O surgical vs spontaneous evacuation was studied separately and combined both.

The study found that:

• When all procedures combined there were increased odds of having a preterm birth, LBW and SGA babies being born after a history of surgical evacuation.
• Vacuum evacuation and sharp curettage were associated with PTB when analyzed in combination. When analyzing separately sharp curettage was associated with higher risk.
• Medical termination was found quite safe and did not result in PTB in subsequent surgery.
• Women with a prior history of spontaneous abortion(SAB) have a higher risk of PTB, as compared to those with no history of SAB.
• A very important observation as a result of meta-analysis is evacuation before 14 weeks of pregnancy (Spontaneous or induced) was not associated with increased risk for PTB.
• Expectant management of missed abortion is an option with ending in spontaneous loss, but sometimes may end up in heavy bleeding requiring immediate evacuation.

References:

http://www.ncbi.nlm.nih.gov/pubmed/24625129

http://www.ncbi.nlm.nih.gov/pubmed/22682464

http://www.who.int/mediacentre/factsheets/fs363/en/

http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm