Updates on management of Preterm Births- News from ACOG Annual Clinical and Scientific Meeting 2016.

The 2016 Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists is ongoing from May 14 to May 17 at the Washington Convention Center in Washington, DC.

Recent clinical trials have led to two important changes in recommendations by ACOG and SMFM on management of preterm births. Steroids are recommended at 23 weeks and at 34-36 weeks to reduce the risks associated with preterm delivery.

Dr. Uma Reddy, MD, MPH, Pregnancy and Perinatology Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health said “All of these changes in practice recommendations will have a real impact on preterm birth.”  “We have already seen a significant decrease in preterm births since a high of 12.8 percent in 2006,” she added. “Preterm birth fell to 11.4 percent in 2013, the last year for which we have complete data. We have had a positive impact in reducing preterm birth.”

The latest recommendations were discussed at Saturday clinical seminar at ACOG annual conference on Saturday May 14, 2016.

 ACOG and the Society for Maternal-Fetal Medicine (SMFM) is now suggesting a single course of steroids for pregnant women starting at 23 weeks who are at risk for preterm birth within seven days. This recommendation is based on a cohort study involving US top 23 academic pediatric centers. It was seen that infants born at 23 to 25 weeks who received antenatal steroids had lower rates of death and lower rates of neurodevelopmental impairment at 18 to 22 months.

The second important recommendation was based on results of the Antenatal Later Preterm Steroids (ALPS) trial reported earlier this year by the Maternal-Fetal Medicine Units Network. A single course of betamethasone in singleton pregnancies between 34 and 36 weeks in women at risk for preterm birth should be given.

The trial showed reduction in the need for respiratory support, reduction in severe respiratory complications, decreased transient tachypnea(TTN), bronchopulmonary dysplasia, and the need for postnatal surfactant. There was no increase in neonatal sepsis, chorioamnionitis, or endometritis, but hypoglycemia was more common in infants exposed to betamethasone. 

These new recommendations are in addition to old recommendations that suggest that all pregnant women between 24 and 34 weeks who are at risk for preterm delivery within seven days receive a single course of corticosteroids. A single rescue course should be considered if a prior course was given at least seven days earlier and the woman remains at risk for preterm birth before 34 weeks.

In summary:

• With the release of this new data and until further guidance is released, administration of betamethasone may be considered in women with a singleton pregnancy between 34 0/7 and 36 6/7 weeks gestation at imminent risk of preterm birth within 7 days. 
• For women in active labor, it is advised to wait for cervical dilatation up-to 3 cm or 75% effacement before administering betamethasone. 
• Tocolysis should not be used in order to delay delivery to allow for administration of late preterm antenatal corticosteroids, nor should an indicated late preterm delivery (such as for preeclampsia with severe features) be postponed for steroid administration.
• All hospitals should utilize standard guidelines for management of hypoglycemia in late preterm newborns.
• Late preterm antenatal corticosteroid administration should not be used in women diagnosed with chorioamnionitis.
• Administration of late preterm antenatal corticosteroids should not be given if the pregnancy was already exposed to antenatal corticosteroids.
• Because the ALPS trial excluded pregnant women with diabetes, multifetal gestations, previous exposure to steroids during pregnancy, or pregnancies with major non-lethal fetal malformations, ACOG is reviewing these topics and will issue any updated clinical guidance as appropriate.

References:

http://www.acogdailynews.com/latest-trials-change-preterm-birth-guidance/

http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Antenatal-Corticosteroid-Administration-in-the-Late-Preterm-Period

http://www.nejm.org/doi/full/10.1056/NEJMoa1516783?af=R&rss=currentIssue

Predicting spontaneous preterm birth in twin pregnancies utilizing cervical length and gestational age: Individual patient data meta-analysis.

Multiple births are steadily climbing all around the world. Developed countries making a significantly higher contribution to this rising rate because of women delaying childbirth, elderly mothers and increased use of ARTs.

US twinning rate rose by 101% from 1980 – 2006. About 68,339 twins were born in 1980 that doubled to 137,085 in 2006. The US current twin birth rate is 33.9 per 1,000 live births.

 According to WHO the rate of singleton preterm birth ranges between 5% to 18% for singleton pregnancy worldwide, the average being 11%, while almost 60% of twins are delivered preterm. About 13% of twins are born before 34 weeks and 7% before 32 weeks.

A multitude of prophylactic therapies have been in use like to gain valuable gestational weeks by supplementing progesterone, vaginal pessaries and strict bed rest without substantially significant results.

The next step was to develop essential biomarkers that can predict the chances of preterm births. Cervical length(CL) has long   been used as a predictive indicator of preterm birth. An earlier review has shown that a CL < or=20 mm at 20-24 weeks' gestation was the most accurate in predicting preterm birth at <32 and <34 weeks respectively. Many other studies have combined fetal fibronectin with CL. 

Studies in singleton pregnancies have also shown that the relationship between CL and spontaneous preterm birth (sPTB) is dependent on the Gestational age (GA) at which the USG is done, a shorter CL early in pregnancy has greater significance than the same measurement at a later GA.

Such studies in twins are few with small sample size and are not comparable. Previous meta-analysis has shown a relationship between CL and sPTB in twins, but did not correlate the GA at screening with prediction of sPTB.

This recent study published in the May, 2016 issue of BJOG is a meta-analysis of independent patient data(IPD), and provides a new estimate in which CL and GA are treated as continuous variables to predict weeks at delivery.

Specific data collected for each patient from the original authors of the study included the exact GA at CL screening, the CL measurement in millimeters and the exact GA at birth in weeks and days.

23 studies met the inclusion criteria, resulting in a total of 6188 transvaginal scans, performed on 4409 twin pregnancies. 

In the first analysis, univariate regression was performed to see what other confounders like maternal age, ethnicity, smoking, BMI, chorionicity, parity and study location affects the GA at birth. 

As second analysis multinomial logistic regression model was derived predicting the probabilities of very early preterm, early preterm, late preterm, and term birth using GA at USG and CL as continuous variables.

Important study results were:

• BMI was the only other variable that correlated significantly with GA at birth in the univariate analysis, but when it was incorporated into multinomial logistic regression model with CL and GA at ultrasound, prediction of GA at birth did not improve.
• A short CL measured at ≤20⁺⁰ weeks by USG indicates a probability of birth significantly earlier than if the same CL was taken at a later GA.
• When screening before 18⁺⁰ weeks, any cervical length <30 mm has a higher risk of sPTB at ≤28⁺⁰ weeks in twins than in singletons.Whereas the best prediction of birth between 28⁺¹ and 36⁺⁰ weeks was provided by screening at ≥24⁺⁰ weeks.
• A 100% probability of preterm birth not occurring before 28 weeks is achieved by CL of 65 mm and 43 mm at ultrasound GA at ≤18⁺⁰ weeks and at 22⁺¹ to 24⁺⁰ weeks, respectively.

In the third analysis, the accuracy of the model to correctly predict term delivery as compared to preterm was assessed. The model has a 68.2% true negative rate, classifying correctly those who were predicted to deliver at ≥36⁺¹ weeks, compared with 26.2, 13.3 and 36.2% correctly predicted to deliver at ≤28⁺⁰, 28⁺¹ to 32⁺⁰ and 32⁺¹ to 36⁺⁰ weeks, respectively (true positive rate).

Although effective intervention for sPTB in twins are limited, the study provides risks of very early, early and late preterm birth, so a personalized cost effective delivery plan, optimal timing of corticosteroids and referring to neonatal unit can be managed. It also justifies serial CL measurements, so that early and late sPTB could be predicted.

To conclude the authors, recommend to start the screening at ≤18⁺⁰ weeks with repeat screening at >22⁺⁰ weeks; this best identifies the patients that may deliver very early at ≤28⁺⁰ weeks as well as the more common later group of sPTB between 28⁺⁰ to 36⁺⁰ weeks. 

References:

http://www.cdc.gov/nchs/fastats/multiple.htm

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

http://www.ncbi.nlm.nih.gov/pubmed/24360590

http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.13575/full

http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.13710/full

Magnesium Sulfate Use in Obstetrics

The source of this  article is : Magnesium sulfate use in obstetrics. Committee Opinion No. 652. American College of Obstetricians and Gynecologists. Obstet Gynecol 2016;127:e52–3.

The U.S. Food and Drug Administration advises against the use of magnesium sulfate injections for more than 5–7 days to stop preterm labor in pregnant women.

Based on this, the category of the drug was changed from ‘A’ to ‘D’ recently, when it was used for more than 5-7 days to prevent preterm labor in pregnant women.

Concerns for fetal and neonatal bone demineralization and fractures associated with long-term in utero exposure to magnesium sulfate prompted this change.

These concerns were based on reports to the FDA’s Adverse Event Reporting System and results from a number of epidemiologic analyses, although these studies have important limitations in designs.

In these population based studies the  average use of  prenatal Magnesium Sulphate was for 9.6 weeks and the dose was  3,700 g, a much longer duration and much higher dose than is currently recommended. The sample size in these studies were also small leading to bias and confounding in the conclusion drawn.

A total 18 cases were reported of fetal and neonatal long bone demineralization and fractures.

So this change of category addresses an unindicated and nonstandard use of magnesium sulfate in obstetric care.

 So, the use of Magnesium Sulphate that is appropriate in clinical practice is:

1. Prevention and treatment of seizures in women with preeclampsia or eclampsia and fetal neuroprotection before anticipated early preterm (less than 32 weeks of gestation) delivery.
2. Short-term prolongation of pregnancy (up to 48 hours) to allow for the administration of antenatal corticosteroids in pregnant women who are at risk of preterm delivery within 7 days.
3. Tocolysis is not recommended beyond 34 weeks of gestation, and is generally not recommended before 24 weeks of gestation but may be considered based on individual circumstances.

References:

https://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Magnesium_Sulfate_Use_in_Obstetrics?IsMobileSet=false