Obstetrics and Gynecology

Twin gestations - di/di

Diamniotic/Dichorionic Twin Gestation

1. What every clinician should know

Clinical features and incidence

According to the division of Vital Statistics of the National Centers for Health Statistics, the United States national twin birth rate reached an all time high of 33.9 per 1000 live births (3.4%) in 2014. Among non-Hispanic black mothers the twin birth rate is 40 per 1000 live births.The risk attributable to this rising twin birth rate cannot be overstated. In 2014, 11% and 59% of twins were born “very preterm” (<32 weeks’ gestation) and “preterm” (<37 weeks’ gestation) respectively, resulting in 10% and 55% of twins being “very low birthweight” (<1500 g) and “low birthweight” (<2500 g). Put another way, more than 50% of the twins born in the United States in 2014 was either preterm or low birthweight.

Of these twin deliveries, approximately 70% are diamniotic/dichorionic (Di/Di) twins. The rate of dichorionic twinning has been rising for the past 30 years, primarily as a consequence of delayed childbearing and assisted reproduction. More than a third of all twin infants born in the United States have been the result of fertility-promoting technology. The vast majority of these are Di/Di twins. It is important to note that since 1997, in vitro fertilization has not been the leaning contributor to the increase in the national twin birth rate. Currently, the greater contributor is non-IVF treatment modalities such as ovulation induction or intrauterine insemination.

The goal of early prenatal care has moved past reliably identifying a twin gestation. All twin gestations should now be further defined as being either dichorionic or monochorionic due to the different risks experienced by the separate twin types. Early diagnosis of the correct type of twin gestation is necessary in order to counsel the patient effectively regarding her specific risks. Fortunately, this correct assignment of chorionicity is possible in the vast majority of cases.

2. Diagnosis and differential diagnosis

Twinning can be suspected in a variety of clinical situations, such as a uterine size greater than dates, maternal hyperemesis, positive personal or family history, significantly elevated beta human chorionic gonadotropin (hCG), or pregnancy as a result of assisted reproduction. However, reliable early detection of twins requires a policy of routine first trimester ultrasound to confirm plurality, viability, and gestational age.

Prior to the widespread use of diagnostic ultrasound, more than 50% of twins were not diagnosed until the onset of labor, and in 30% the second twin was not discovered until after the delivery of the first twin. In the RADIUS trial, the control group received selective, rather than routine ultrasound; in that group of women, more than one third of twins were not diagnosed until after 26 weeks’ gestation and almost 10% were not diagnosed until labor.

Although the RADIUS trial was not powered to identify significant differences in the multiple gestation subgroup, it revealed an almost 50% reduction in composite adverse perinatal outcomes among the twins routinely screened.

Ultrasound

First trimester

Ultrasonography is extremely reliable in differentiating dichorionic from monochorionic twin gestations; however, this determination gets more difficult as pregnancy progresses. Prior to 10 weeks, counting the gestational sacs will differentiate a dichorionic from a monochorionic gestation. The sonographer should be careful to confirm the presence of either a fetus or yolk sac within each gestational sac. Anembryonic sacs are frequently misdiagnosed as "vanishing twins" when they actually represent such things as subchorionic hemorrhage, cystic fibroids, endometrial polyps, or excessive transducer pressure on the uterus.

Between 10 and 14 weeks, the presence of separate placentas confirms dichorionicity. To distinguish a single monochorionic placenta from a fused dichorionic placenta, the presence of a "twin peak" or lambda sign will identify the dichorionic gestation virtually 100% of the time. In a monochorionic gestation the amniotic membranes will come flush against the chorionic surface (T-sign).

Second trimester

After 14 weeks, the ability to identify fetal gender helps with differentiating a fused dichorionic (fraternal opposite sex) twin set from a monochorionic (identical same sex) twin set. In the second trimester the yolk sacs have disappeared, the dividing membrane progressively thins, the likelihood of placental fusion increases, and fetal growth can obscure visualization. However, despite these increased difficulties, the "twin-peak" sign remains highly reliable, and using a composite of available ultrasound findings, it is still possible to differentiate Di/Di from Mono/Di twin sets in over 90% of cases.

Laboratory studies

First trimester

The Di/Di twin gestation requires all the same prenatal labs as does a singleton gestation. Particular attention should be given to the Hgb/Hct, as mothers of multiple gestations experience high rates of anemia, usually iron deficiency. A first trimester Hgb less than 12.0 g/dl with low or low normal MCV and MCH indices should prompt iron supplementation in addition to the usual prenatal vitamins. If the MCV and MCH are low, the other possibility is a hemoglobinopathy, and a hemoglobin electrophoresis would be advised. If the MCV and MCH are normal or high and the Hgb is less than 12.0 g/dl, the work-up should also include a folate level and B-12 measurement.

There is an increased recognition that the majority of pregnant women, and virtually all pregnant women of color, are vitamin D deficient or insufficient. Emerging data suggests that maternal 25-OH vitamin D levels greater than 40 ng/mL are associated with multiple health benefits including reduced rates of preterm birth (PTB), less gestational diabetes, and a lower risk of childhood atopy and asthma. Vitamin D deficient women require supplementation with between 4000 and 6000 international units of vitamin D/day.

The mother of a multiple gestation should also be offered first trimester aneuploidy screening. The first trimester screen may be particularly advantageous for the Di/Di twins compared to a second trimester quad screen because it incorporates the nuchal translucency measurement that will be specific to each individual twin. The second trimester quad screen relies solely on maternal serum markers, and detection of aneuploidy in one twin can be obscured by the euploid co-twin, reducing sensitivity. The sensitivity of both the first trimester aneuploidy screen and the second trimester quad screen are believed to be lower than the corresponding sensitivity for singleton gestations.

Another alternative for first trimester aneuploidy testing is the use of fetal cell-free DNA. Fetal cell-free DNA is obtained from a maternal blood sample and analyzed for the presence of specific aneuploidies. Non-invasive prenatal testing is both more sensitive and specific than maternal serum first trimester screening using biomarkers and a nuchal translucency measurement. However, while the test can identify an aneuploid gestation, it cannot determine which of the two dizygotic fetuses may be affected. Further diagnostic testing will be required in this situation. At present, the 2015 American Congress of Obstetricians and Gynecologists (ACOG) and Society for Maternal-Fetal Medicine (SMFM) committee opinion regarding fetal cell-free DNA testing does not recommend its use in twin gestations due to uncertainties regarding sensitivity and specificity. However, we do use this testing approach in our twin gestations and we anticipate that those published recommendations will be changed very soon.

First trimester maternal hCG levels are significantly higher in multiples compared to singletons. There are no clinical indications to assay the hCG level; however, high hCG levels are believed to be related to an increased prevalence of hyperemesis gravidarum and mild hyperthyroid-like symptoms (chemical hyperthyroidism) in twins.

Second trimester

Di/Di twin gestations are at higher risk for gestational diabetes mellitus (GDM) because of greater placental production of human placental lactogen (HPL). Indeed, epidemiological studies suggest that the risk of GDM increases 1.8-fold for each additional fetus. The ACOG recommends that all pregnant women be screened for GDM between 24-28 weeks’ gestation using the 1-hour 50 gram glucose load test. A standardized 3-hour oral glucose tolerance test (OGTT) is recommended for diagnosis if the glucose load test results are greater than 140 mg/dl. This is the practice that we follow, although some would suggest doing the 1-hour glucose load test earlier at 20 weeks’ gestation, due to the higher risk. A second trimester quad screen for aneuploidy screening can be performed if the first trimester screen was missed.

Third trimester

As previously mentioned, anemia complicates as many as 25% of all twin gestations. These same twins are at increased risk for intrapartum and postpartum hemorrhage. We routinely check an early third trimester complete blood count (CBC) and ferritin level. If the results indicate an iron-deficiency anemia, we start an iron supplement. If the anemia is severe and the patient is non-compliant with oral iron, we will start parenteral iron until adequate iron replacement has been achieved. There are both intramuscular and intravenous preparations for iron administration. Patients identified with severe microcytic hypochromic anemia should also be asked about the possibility of pica.

If pre-eclampsia is suspected, a CBC, platelet count, and liver transaminases should be obtained as part of the workup. Pre-eclampsia among twin gestations is more frequently severe and more frequently complicated by HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome, compared with singleton pregnancies. When preterm labor (PTL) is suspected or if the mother has increased symptoms potentially related to PTL, we will use the fetal fibronectin test to differentiate the innocuous from the consequential. The negative predictive value for the fetal fibronectin test remains extremely high (greater than 95% for delivery within the next 1-2 weeks) even when used in women with Di/Di twin gestations.

Genetic prenatal diagnostic testing

More than 90% of Di/Di twins are dizygotic, meaning that the two twins are genetically unique (separate eggs fertilized by separate sperms). Prior to any subsequent genetic risk screening, the baseline aneuploidy risk will be the mother's age-related risk, and that risk will be additive for each fetus, as each is an independent genetic event. For example, for a mother with dizygotic Di/Di twins and a singleton age-related risk of 1 in 100 (1%) for aneuploidy, the risk that either of her twins could have a chromosomal defect would be 1% + 1% = 2%. Approximately 10% of Di/Di twins will be monozygotic, resulting from the early splitting (within the first 3 days) of a single embryo. Both fetuses will have arisen from the same egg and sperm, and therefore, will be genetically identical (and have the same sex as confirmed by ultrasound). The baseline genetic risk for a monozygotic twin gestation will be the mother's age-related risk, and it will be the same for both fetuses. For example, if the mother's age-related risk is 1%, then each fetus carries the same 1% risk and both fetuses will either be affected or unaffected.

Non-invasive prenatal testing analyzes cell-free DNA circulating in maternal blood. This represents a new option in the prenatal testing paradigm for trisomy 21 and selected other fetal chromosomal aneuploidies. DNA from the placenta circulates in maternal blood. Unlike intact fetal cells which can persist for years after a pregnancy, circulating cell-free DNA results from the breakdown of placental syncytio-cytotrophoblastic cells clears from the maternal circulation within hours. Fetoplacental DNA, therefore, is detectable during pregnancy and represents DNA from the current fetus. Testing can be done any time after 10 weeks; typically, between 10-14 weeks’ gestation. Non-invasive prenatal testing technology has been validated in singleton pregnancies at high risk for trisomy 21 with the following indications: 1) advanced maternal age; 2) an abnormal serum screen; 3) personal or family history of aneuploidy; or 4) ultrasound findings suggestive of aneuploidy. Commercial laboratories will currently accept samples from either high-risk or low-risk pregnancies. Additionally, most will offer this testing for twin pregnancies. While the sensitivity and specificity is believed to be as good for twin pregnancies as it is for singletons, the tests will not be informative as to which fetus in a dichorionic gestation is affected.

All laboratories offer non-invasive prenatal testing for trisomy 21, trisomy 18, trisomy 13, and sex chromosome abnormalities. At least 99% of all pregnancies with trisomy 21 can be detected using this test. However, up to 1 in 100 pregnancies with trisomy 21 will have a normal result and be missed on a screening. The false positive rate is approximately 0.2%, meaning 1 in about 500 of unaffected pregnancies are reported as positive “or consistent with” trisomy 21. For that reason, it is recommended that chorionic villus sampling (CVS) or amniocentesis be considered after an abnormal result to confirm the presence of a chromosomal abnormality. Similar detection rates are available for trisomy 18. There is less confidence in non-invasive testing as a screen for trisomy 13. Detection rates between 78-92% have been reported, meaning that 8-22 out of 100 with an affected fetus will be missed. The false positive rate is estimated to be about 1%, so 1 out of 100 unaffected pregnancies will be reported as positive for trisomy 13. Fortunately, ultrasonic assessment of the fetus is highly effective in identifying fetal abnormalities associated with trisomy 13, however, confirmatory testing is recommended. A recent study involving 189 twins who received non-invasive prenatal diagnostic testing had favorable results. 9 of 9 affected pregnancies received a positive screening result for trisomy 21. One out of two of the affected pregnancies received a positive result for trisomy 18 and there were no false positives in the cohort.

Options for confirmatory testing include the CVS test, which can be done transcervically or transabdominally between 10-14 weeks’ gestation, and genetic amniocentesis performed after 15 weeks’ gestation. Diagnostic testing for twins likely carries a small increase in risk compared with singletons regardless of the test selected. Risk estimates between 1-2% for twin CVS and up to 1% for twin amniocentesis have been suggested.

Twin CVS procedures are technically challenging, and it is harder to ensure that each fetus is individually tested without contamination from one fetus to the other. A twin CVS procedure should only be attempted by providers with extensive experience in chorionic villus sampling.

Twin amniocentesis can also be challenging, with the biggest concern being to ensure that both sacs are sampled and that adequate documentation is provided to make certain that the affected fetus can be later identified if discordant results are found. The most commonly used technique is to inject a dilute solution of indigo carmine (1 cc diluted in 10 cc of normal saline) into the amniotic sac after the first fetus is sampled.

When the second fetus is sampled, there should not be any blue tinge to the aspirated amniotic fluid. Methylene blue should be avoided because it has been associated with fetal gastrointestinal (GI) tract atresia believed to be secondary to the vaso-constrictive effects of methylene blue swallowed by the fetus.

3. Management

Maternal nutrition

One of the most important management recommendations is also one of the simplest. Maternal nutritional demands are magnified by the presence of multiple fetuses. The accelerated depletion of maternal nutritional reserves has been associated with alterations in fetal growth and shortening of gestational length. Specific recommendations regarding the augmented nutritional requirements in a twin gestation have been reviewed in an expert series publication by the Society for Maternal-Fetal Medicine in Obstetrics and Gynecology in 2009. The constrained growth of multiples creates a situation where modifiable factors such as maternal nutrition can have a significant positive impact on outcome.

Clinically, the rate and pattern of maternal weight gain can be used as a measure of adequate nutrition. The influence of early and adequate maternal weight gain on subsequent twin growth and perinatal outcomes is most pronounced in underweight and normal weight women. Low maternal pre-gravid weight and/or a low maternal weight gain is also associated with increased risk of premature birth in twins. It is believed that adequate early weight gain results in improved maternal nutrient stores that become important late in pregnancy as a nutrient reserve when fetal demands are increased. In addition, early maternal weight gain may also contribute to improved placental growth, which helps to sustain the twins later in pregnancy.

In one prospective cohort trial, achievement of the 2009 Institute of Medicine (IOM) guidelines regarding weight gain in twin pregnancies was assessed for its impact on perinatal outcome. Women with twin pregnancies and normal pre-pregnancy body mass indexes (BMIs) who had an appropriate gestational weight gain per IOM guidelines, had clinical outcomes far superior compared to those women who failed to gain the recommended maternal weight. Women who met IOM weight gain recommendations had significantly lower rates of spontaneous PTB, greater birth weights overall, lower rates of intrauterine growth restriction, and were more likely to have twin neonates who weighed more than 2500 grams.

BMI-specific weight gain guidelines have been developed for twin gestations. We prefer to use the guidelines developed by Luke, et al. The IOM guidelines were developed based on the Luke data, but because of small revisions to the BMI categories, the IOM guidelines are not exactly the same and do not provide recommendations for underweight women who are likely the highest risk group. Optimal rates of twin fetal growth and birth weight have been achieved with maternal weight gains of 50-62lbs for underweight women (BMI <19.8); 40-45 lbs for normal weight women (BMI 19.8-26.0); 38-47 lbs for overweight women (BMI 26.1-30.0); and 29-38 lbs for obese women (BMI >30).

Prospective cohort trials emphasizing nutritional interventions for women with twins or comparing those who did or did not meet advised maternal weight gain recommendations, have consistently demonstrated improved obstetrical and neonatal outcomes including increased birth weight by at least 250 g/twin-fetus, and a longer length of gestation by approximately one week. Specifically, rates of early PTB less than 32 weeks’ gestation are significantly reduced among women carrying twins with appropriate weight gain. These improvements in fetal growth and gestational age at delivery have been linked to improved composite neonatal outcomes, less frequent admission to the neonatal intensive care unit (NICU), and shorter neonatal hospital length of stay. Improved maternal nutrition and fetal growth is also anticipated to contribute to improved childhood and adult health based on the Barker hypothesis.

Preterm birth surveillance and prevention

We routinely perform a transvaginal cervical length (TVCL) measurement on all of our twins during their ultrasound examinations between 18-24 weeks’ gestation. A mid-trimester TVCL>35 mm has been associated with only a 3% risk of spontaneous PTB <34 weeks’ gestation. Identifying a mid-trimester TVCL >35 mm provides significant reassurance and allows the avoidance of unnecessary limitations of maternal activity or travel, discontinuation of work, or prohibitions against sexual relations.

Alternatively, a shortened mid-trimester TVCL of <25 mm has been shown to correlate powerfully with an increased risk of early preterm delivery in twins. This relationship is a continuum with a greater risk for early preterm delivery as the cervix shortens. When a short cervix (<25 mm) is identified in a twin gestation, the management options are limited. Reduced activity and increased rest are probably the most commonly prescribed interventions among twins despite a paucity of evidence supporting its efficacy. A recent secondary analysis was performed of a prospective randomized trial of 17 alpha hydroxyprogesterone caproate for prevention of PTB among nulliparous singleton gestations with cervices <30 mm by mid-trimester ultrasonography. Women were asked weekly if they had been put on “any activity restriction” by their care provider. After controlling for multiple confounding factors, PTB was more frequent among those women who were advised to restrict their activities (AOR 2.37; 37; 95% CI 1.60-3.53). Despite the absence of any prospective randomized or cohort studies supporting its use, there may be other reasons to endorse restriction of strenuous activity and rest in multiples. Tocodynamometry studies have shown that maternal rest is associated with a reduction in uterine contraction frequency.

A meta-analysis of 29 studies demonstrated a significantly increased risk of adverse pregnancy outcome, including PTB, associated with physically demanding work, prolonged standing, and shift- or night-work. Although these studies addressing occupational fatigue involved singleton gestations, it would be naive to assume that a similar, if not magnified, effect did not occur in multiples. Further research is clearly needed to define the impact of restricted activity and increased rest in twins with a shortened cervical length. Having said this, there are several studies which demonstrate that routine hospitalization does not improve perinatal outcome or reduced preterm delivery in women carrying a twin gestation.

When confronted with a mid-trimester TVCL <25 mm we do initiate treatment with daily vaginal progesterone. Our preference is 200 mg of Prometrium vaginally at bedtime. The evidence for the efficacy of vaginal progesterone in twins with a short cervical length is limited. However, two recent meta-analyses using individual participant data from prospective, placebo-controlled, randomized trials of vaginally administered progesterone in twin gestations with a cervical length <25 mm, demonstrate a significant reduction in adverse composite neonatal outcomes in the treatment group and a borderline, but nonsignificant, reduction in early PTB. The effect estimates were similar to that previously found in prospective, randomized trials (PRTs) and meta-analyses of singleton gestations with a short cervical length (<25 mm) treated with vaginal progesterone.

In unselected women with uncomplicated twin gestations, vaginal progesterone does not prolong pregnancy or improve perinatal outcomes. The benefit of vaginal progesterone appears limited to the subgroup of twin mothers with a short cervical length. This may have biologic plausibility as a short cervix might be an early sign of the onset of parturition. These findings, however, should be interpreted with caution because they are derived from post hoc analyses of studies with relatively small subgroups of twin gestations with a short cervical length. However, these findings should stimulate further research on progesterone in twin pregnancies with a short cervix.

Conversely, based on multiple prospective randomized trials and meta-analyses, there is no evidence that either beta-adrenergic tocolytics or 17 alpha hydroxyprogesterone caproate are effective in preventing PTB, either in unselected twin gestations, twins with a shortened cervical length, or symptoms of PTL. When confronted more acutely with preterm delivery risk, antenatal corticosteroids are administered to reduce the incidence of respiratory distress syndrome, intraventricular hemorrhage, and other complications of prematurity. The National Institutes of Health (NIH) recommendations advise administration of corticosteroids with PTL prior to 34 weeks and to women with preterm premature rupture of membranes (PPROM) at <30-32 weeks, regardless of plurality.

A recent NIH-sponsored trial identified a benefit associated with cerclage placement for women with singleton gestations complicated by a prior singleton PTB, and found to have a mid-trimester TVCL <25mm (and especially a TVCL <15 mm). Unfortunately, ultrasound-indicated cerclage has not been demonstrated to be of benefit in twin gestations with a shortened cervical length. A meta-analysis of available randomized trials, as well as our own prospective trial, demonstrated no benefit to cerclage placement in twins with a TVCL <25 mm. We restrict our use of cerclage to those twins with either a classic history-based indication of cervical insufficiency, an exam-based indication with a dilated cervix or membranes visible at the external os, or a progressively shortening cervix (<15 mm) at a pre-viable gestation that has failed both bed rest and vaginal progesterone.

It is cautioned that these cerclage recommendations are supported only by relatively small retrospective cohort studies. Roman and colleagues reported on a planned subgroup analysis of asymptomatic twin pregnancies with a TVCL <15 mm where cerclage placement was associated with a 4-week prolongation of pregnancy, significant reduction in spontaneous PTB <34 weeks, and a 58% lower admission rate to the NICU compared to controls. Given the paucity of evidence supporting an operative approach to this problem, emergency cerclage placement should be rarely performed and only after careful and extensive patient counseling and consent.

There has been a recent resurgence of interest in the use of the vaginal pessary to reduce the risk of PTB in multiple gestations. The exact mechanism by which a cervical pessary may generate a beneficial effect is unknown. Pessaries may relieve direct pressure on the internal cervical os by redistributing the gestational weight onto the vaginal floor or retrosymphyseal osteomuscular structures. Others believe the pessary may compress the cervical canal, preventing loss of the cervical mucus plug, which plays a role in preventing ascending infection and a resulting inflammatory immunological response.

A multicenter, open-label prospective trial in 40 Dutch hospitals recruited 808 women with a twin gestation between 12-20 weeks’ gestation. These women were randomized to either an Arabin pessary (N=401) or a standard care control group (N=407). In the entire cohort, there was no difference in a composite poor perinatal outcome between the groups. However, a planned subgroup analysis of multiple gestations with a cervical length at the 25th percentile (38 mm) or less revealed more favorable findings. Both maternal (RR 0.40; 95% CI 0.19-0.83) and child (RR 0.42; 95% CI 0.19-0.91) poor perinatal outcomes were significantly reduced in the subgroup of twins with a short cervix who received a pessary. In addition, the gestational age at delivery was significantly greater in the pessary group and there was a lower risk of delivering before both 28 and 32 weeks’ gestation. The cervical pessary did not effectively prevent poor perinatal outcome or PTB among unselected twin gestations. However, in the subgroup of women with a cervical length <25th percentile, the pessary group had better perinatal outcomes and fewer early PTBs. These findings need to be confirmed in future prospective trials of women with a twin pregnancy and a short cervical length.

A large multicentre PRT of cervical pessary to prevent spontaneous early PTB enrolled more than 1000 unselected twin gestations between 20 and 24 weeks' gestation. In this unselected twin pregnancy population, the routine use of a cervical pessary did not improve any measure of prematurity. In February of 2016, Goya and colleagues reported on the use of the Arabin pessary to prevent PTB in twin pregnancies with a sonographic short cervix (PECEP-Twins). PECEP-Twins was a prospective, open-label, multicenter, randomized trial conducted in five Spanish hospitals. One hundred and thirty-seven women carrying twins were identified with a TVCL <25 mm and were randomly assigned to receive a cervical pessary or expectant management. Pessary use reduced the rate of spontaneous PTB <34 weeks of gestation by almost 60% from 39.4% (26/66) to 16.2% (11/68). Pessary use was associated with a significant reduction in birthweight <2500 g, but no difference in composite neonatal morbidity or mortality.

Most recently, Fox and coworkers reported on 21 women carrying twins treated with vaginal progesterone and an Arabin pessary,who were retrospectively matched 3:1 to 63 twin gestations based on gestational age at diagnosis and cervical length treated with vaginal progesterone alone. Pessary use was associated with a significant reduction in spontaneous PTB <32 weeks from 28.6% (18/63) to 4.8% (1/21), and it also lowered the incidence of severe neonatal morbidity from 34.9% (22/63) to 9.5% (2/21).

All of these studies are provocative and suggest that the pessary may be an option for twin gestations in mothers found to have a significantly shortened cervix in the mid-trimester. Although it can be obtained from Europe, the Arabin pessary is not yet approved by the FDA for use in the United States. This is important because it was the device used in successful pessary trials. Further prospective, multicenter trials are currently ongoing.

Third trimester fetal surveillance

The risk of third trimester stillbirth is higher for twins than it is in singletons. Although no prospective randomized trial endorses the routine use of antenatal fetal surveillance, we nevertheless institute routine fetal testing at 34 weeks’ gestation for dichorionic twin gestations. We initiate similar testing at 32 weeks for monochorionic/diamniotic twins. Both the nonstress test (NST) and the biophysical profile (BPP) are as reliable for twin gestations as they are for singletons. Testing is initiated sooner if the twins are complicated by fetal growth restriction (FGR), severe discordance, elevated umbilical artery Doppler's, abnormal amniotic fluid volumes, monoamnionicity, or mild preeclampsia. Generally, fetal testing is performed on a weekly basis, except in the presence of intrauterine growth restriction(IUGR), abnormal Doppler studies, or preeclampsia which might necessitate twice-weekly or more frequent testing.

We routinely perform ultrasonography every 4 weeks in the second and third trimester for the dichorionic twin gestation to follow fetal growth and other parameters. The inability of ultrasound to reliably diagnose either IUGR or growth discordance among twins is probably the major reason to recommend routine fetal testing of all multiples. A long-standing controversy has been whether or not growth expectations should be the same for twin gestations as it is for singletons. In 2015, the National Institute of Child Health and Human Development (NICHD) published the results of its National Fetal Growth Study.That study involved the prospective follow-up of 2334 healthy women with low-risk, singleton pregnancies from twelve different perinatal centers. The study population was equally distributed between non-Hispanic whites, non-Hispanic blacks, Hispanics and Asians who underwent longitudinal fetal growth measurements using ultrasound throughout gestation. Racial/ethnic-specific fetal growth standards were established for each of the four groups and demonstrated improvements in the precision of evaluating fetal growth.

As a corollary to the NICHD National Fetal Growth Study, a prospective cohort of 171 women with dichorionic twin gestations was recruited from eight participating centers between 2012 and 2013. The objective was to empirically define the trajectory of fetal growth in dichorionic twins using longitudinal 2-dimensional ultrasonography, and compare the fetal growth trajectories for dichorionic twins with the new singleton growth standards. Each woman with dichorionic twins underwent a median of five ultrasounds. The 50th percentile abdominal circumference and estimated fetal weight trajectories of twin fetuses diverged significantly from singleton standards beginning at 32 weeks of gestation, while biparietal diameter in twins was smaller from 34 -36 weeks. There were no differences in head circumference or femur length. The mean HC/ACratio was progressively larger for twins compared with singletons beginning at 33 weeks, indicating a comparatively asymmetric growth pattern.

At 35 weeks, the average gestational age at delivery for twins -the estimated fetal weights for the 10th, 50th, and 90th percentiles - were 1960, 2376, and 2879 grams for dichorionic twins compared to 2180, 2567, and 3022 grams for singletons. At 32 weeks, the initial week when the mean estimated fetal weight for twins was smaller than that of singletons, 34% of twins would be classified as small for gestational age (SGA) using a singleton, non-Hispanic white standard. By 35 weeks, 38% of twins would be classified as SGA.

The findings of the NICHD National Fetal Growth Twins study suggests a comparatively asymmetric growth pattern in twin gestations, initially evident at 32 weeks. This finding is consistent with a concept that the intrauterine environment becomes constrained in its ability to sustain expected growth in twin fetuses. Near term, nearly 40% of twins would be classified as SGA based on a singleton growth standard. In our practice, we follow our twin gestations using an expected growth standard for singleton fetuses and maintain awareness of the typical time points when twin growth diverges from that of a singleton. The inability of twin gestations to maintain a normal singleton growth trajectory in a large percentage of cases is another appropriate indication for routine third trimester fetal surveillance.

Based on our experience with 768 twin gestations (601 DC and 167 MC) cared for at our institution at 34 or more weeks’ gestation, the prospective risk of intrauterine fetal death (IUFD) was 0.17% (N=1) for dichorionic twins and 0% for monochorionic twins using the above described approach to fetal surveillance.

Timing of delivery

The ideal timing of delivery for the uncomplicated dichorionic twin gestation appears to be with the achievement of 38 weeks of gestation. The nadir of fetal mortality for all twins occurs between 36-37 weeks’ gestation, and both fetal and neonatal mortality rates begin to rise in twins extended beyond 38 weeks. Unfortunately, the hypothesis that elective delivery of uncomplicated dichorionic twins at 38 weeks’ gestation is ideal has not been subjected to prospective randomized testing. However, based on evidence from population-based data, and retrospective and prospective cohort trials, current consensus-based expert opinion recommends delivery of uncomplicated dichorionic twins at 38 weeks’ gestation without the necessity for fetal maturity testing. This also corresponds to the nadir of neonatal morbidity in dichorionic twin gestations. Earlier delivery based on the presence of complications such as FGR, significant discordance, polyhydramnious, preeclampsia, or any other significant alteration in maternal-fetal condition may be indicated based on usual obstetrical indications.

Mode of delivery

The mode of delivery is another area of clinical controversy. There is a strong consensus that cesarean delivery is indicated if the first twin is presenting as a breech or transverse lie. Alternatively, when both twins are in a cephalic presentation, there is no evidence that outcomes are improved by cesarean delivery. In fact, elective cesarean has been associated with a greater risk of neonatal respiratory morbidity. When the first twin is in a cephalic presentation and the second twin is non-cephalic, recommendations are more complex. A small randomized trial by Rabinovici and colleagues did not identify any difference in outcome between cephalic/breech twins delivered by planned cesarean versus a cephalic vaginal delivery of twin A and a breech extraction of twin B. That study, however, was limited to just over 30 twin gestations in each group. Subsequently, several cohort studies have reported a reduced risk of adverse perinatal outcomes for both twins or the second twin only, when term or near-term twins are delivered by planned cesarean.

In 2013, the Twin Birth Study was published. The Twin Birth Study was a large randomized trial of planned cesarean or vaginal delivery for twins after 32 weeks’ gestation with the first twin in a cephalic presentation. A total of 1398 women (2795 fetuses) were randomly assigned to planned cesarean and 1406 women (2812 fetuses) to planned vaginal delivery. The rate of cesarean delivery was 90.7% in the planned cesarean group and 43.8% in the planned vaginal delivery group. In both groups, approximately 60% of the twins were both cephalic, and in approximately 40% the first twin was cephalic and the second twin was non-cephalic. There was no significant difference in the primary outcome of composite fetal or neonatal death or serious neonatal morbidity between the planned cesarean (2.2%) and planned vaginal delivery groups (1.9%; OR 1.16; 95% CI 0.77-1.74). The primary outcome was not influenced by any other relevant variables including presentation of the 2nd twin (cephalic vs. non-cephalic; p =.51) or chorionicity (DC vs. MC; p =.15). There was a higher risk of an adverse perinatal outcome for the second twin compared to the first; however, planned cesarean did not reduce this risk. Planned cesarean was not associated with a higher or lower risk of maternal death or serious maternal morbidity. This may be explained, in part, by the high rate of cesarean in the planned vaginal delivery group.

In 2015, a follow up to the Twin Birth Study was published based on a 3-month questionnaire with a 92% response rate. Outcomes at 3 months postpartum did not differ between women randomized to planned cesarean versus planned vaginal delivery. The mode of delivery was not associated with problematic urinary incontinence, urinary incontinence that affected quality of life, fatigue, or postpartum depression. Contrary to previous studies, breastfeeding rates were not increased in the planned vaginal delivery group.

Finally, in 2016, the Twin Birth Study published a 2-year neurodevelopmental follow-up study involving 83% of the original 5565 fetuses/infants enrolled in the randomized trial. There was no significant difference in the outcome of death or neurodevelopmental delay: 5.99% in the planned caesarean vs. 5.83% in the planned vaginal delivery group (OR 1.04; 95% CI 0.77-1.41; p=0.79). The authors concluded that a policy of planned cesarean delivery provides no benefit to children at age 2 compared with a policy of planned vaginal delivery in uncomplicated twin gestations after 32 weeks of gestation where the first twin is in a cephalic presentation.

4. Complications

Fetal/neonatal

The biggest risk confronting twins is PTB. The average twin delivers between 35 and 36 weeks’ gestation at a mean birth weight of 2300 to 2500 grams. Approximately half of twin sets deliver prior to term, one in six deliver at 32 weeks or earlier, and one in 10 is very low birth weight (VLBW) less than 1500 grams. Twins are responsible for about 15% of all cases of cerebral palsy, one fourth of all VLBW deliveries, one fifth of all low birth rate (LBW) deliveries and 13% of all PTBs in the United States.

About 10% of all NICU admissions in the United States are the product of a twin gestation. Those twins are responsible for about 14% of all respiratory distress syndrome (RDS), 12% of all grade III or IV intraventricular hemorrhage (IVH) and 10% of all cases of neonatal sepsis.

FGR is also a major risk for twin gestations. Allowing for the normal growth of two fetuses is a nutritional and placental challenge for many women. By term, more than one third of twins are SGA. As a consequence of both restricted growth and PTB, twins experience rates of fetal, neonatal and infant mortality that are 6-8-fold higher than for singleton gestations.

Fetal anomalies are 2-3-fold more common in multiple gestations, but most of this risk is due to midline structural defects and vascular disruptions associated with monochorionic gestations. However, dichorionic twins are at increased risk for crowding abnormalities such as clubbed feet. Lastly, there are two fetuses as opposed to one, and discordance for fetal anomaly is the rule (80-90%) rather than the exception.

Maternal

Maternal complications beyond those associated with PTB are multiple and include a 20-40% risk of anemia, a 10-20% risk of pre-eclampsia, a 6-10% risk of gestational diabetes, a 5-10% risk of urinary tract infection (UTI), and a 25-35% risk of antepartum hospital admission for some reason other than delivery.

Intrapartum, the risk of cesarean delivery exceeds 50%, and there are associated higher risks of postpartum hemorrhage, blood transfusion, and endometritis. Compared with women carrying a singleton, women with twins are at increased risk for ICU admission, for peri-partum cardiomyopathy, and are at 3-4-fold greater risk of maternal mortality.

5. Prognosis and outcome

Maternal and fetal/neonatal outcomes

Twin gestations represent one of the most common high risk conditions encountered during pregnancy. Early in gestation, the mother and family need to be counselled regarding the increased risks associated with dichorionic twins. The increased frequency of maternal complications associated with twins is described in the section above. It is important to make mothers aware of the high rate of cesarean delivery (>50%) and the greater risks of potentially life-threatening complications such as pulmonary embolism, hypertensive complications, post-partum hemorrhage, or peri-partum cardiomyopathy.

Fetal/neonatal complications are also magnified by increased fetal plurality and are described in the above section as well. Pre-maturity and growth restriction are two of the most commonly encountered complications in twins. Twins are responsible for a disproportionate share of the neonatal morbidity seen in the United States. These complications result in a neonatal mortality rate that is approximately 5% while the comparable singleton rate is closer to 0.5%. Infant mortality rates (up to one year of age) are also about 5-6-fold higher for twin gestations compared to singleton gestations. Long term neurological morbidity such as cerebral palsy can be expected in approximately one twin out of every ten twin gestations, and in one triplet out of every three triplet gestations. Twin gestations are responsible for about 15% of all cases of cerebral palsy in the United States.

Impact on long-term health

Twin gestations have a relatively small effect on long-term maternal health in the absence of any of the complications described above. Peri-partum cardiomyopathy, acute fatty liver of pregnancy, severe diastasis of the rectus muscles, severe pre-eclampsia, and cesarean birth may all carry long-term maternal health risk. The high rate of FGR is also likely to be contributory to long-term adult health complications as predicted by the Barker hypothesis. Dizygotic, dichorionic twins also carry an increased familial risk of recurrence (1.5-2-fold increased risk).

6. What is the evidence for specific management and treatment recommendations?

Goodnight, W, Newman, R. "for the Society for Maternal-Fetal Medicine. Optimal nutrition for improved twin pregnancy outcome". Obstet Gynecol. vol. 114. 2009. pp. 1121-34.

(This article reviews the caloric, protein, carbohydrate, fat, and individual nutrient needs for twin gestations compared to singletons. Women who meet the recommended weight gain thresholds experience longer gestations and higher twin birth weights, compared to women who either fail to achieve or exceeded the established weight gain recommendations for twins.)

Huang, X, Zheng, J, Chen, M. "Non-invasive prenatal testing of trisomies 21 and 18 by massively parallel sequencing of maternal plasma DNA in twin pregnancies". Prenat Diagn. vol. 34. 2014. pp. 335-40.

(Among 189 pregnant women carrying twins, there were nine cases of trisomy 21 and two cases of trisomy 18 confirmed by karyotyping. Plasma DNA sequencing correctly identified all nine cases of trisomy 21 and one case of trisomy 18. The discordant of trisomy 18 was an unusual feature of monozygotic twins with discordant fetal karyotype [1 normal and the other trisomy 18]. The sensitivity and specificity of maternal plasma DNA sequencing for trisomy 21 were both 100%, and for fetal trisomy 18 were 50% and 100%, respectively.)

Fox, NS, Rebarber, A, Roman, AS, Klauser, CK. "Weight gain in twin pregnancies and adverse outcomes: Examining the 2009 Institute of Medicine guidelines". Obstet Gynecol. vol. 160. 2010. pp. 100-6.

(In women with twin pregnancies and normal starting BMI's, appropriate weight gain during pregnancy is significantly associated with improved outcomes. Women who met IOM weight gain recommendations had lower rates of spontaneous PTB [3.4% vs. 11.5%], greater birth weights [2582 g vs. 2370 g], and were more likely to have twin neonates >2500 g [38.8% vs. 22.5%].)

Luke, B, Hediger, ML, Nugent, C. "Body mass index specific weight gains associated with optimal birth weights in twin pregnancies". J Reprod Med. vol. 48. 2003. pp. 217-24.

(Using ultrasound measures of fetal growth and twin birth weights, BMI-specific weight gain guidelines were developed for the gestational periods of 0-20 weeks [early gestation], 20-28 weeks [mid gestation], and after 28 weeks [late gestation]. Among a cohort of more than 2500 twins, optimal rates of fetal growth and birth weight were achieved with lesser weight gains among overweight and obese women, but required greater weight gain in underweight or normal women.)

Luke, B, Misiunas, R, Anderson, E. "Specialized prenatal care and maternal and infant outcomes in twin pregnancy". Am J Obstet Gynecol. vol. 189. 2003. pp. 934-8.

(A prospective cohort trial of twins at the University of Michigan evaluated the effect of intensive nutritional education, provision of heme-iron rich protein, tracking of maternal weight gain, and micronutrient supplementation [Ca/Mg/Zn]. The intervention group showed significant improvements in the length of gestation, birth weight, obstetrical outcomes [preeclampsia, pPROM, and PTB], and neonatal outcomes [VLBW, NICU admission, composite morbidity].)

Imseis, HM, Albert, TA, Iams, JD. "Identifying twin gestations at low risk for preterm birth with a transvaginal ultrasonographic cervical measurement at 24-26 weeks’ gestation". Am J ObstetGynecol. vol. 177. 1997. pp. 1149-55.

(This was a retrospective analysis of 85 twin gestations that underwent TVCL evaluation between 24-26 weeks. Only 3% of twins with a TVCL >35 mm delivered spontaneously prior to 34 weeks’ gestation.)

Souka, AP, Heath, V, Flint, S. "Cervical length at 23 weeks in twins in predicting spontaneous preterm delivery". Obstet Gynecol. vol. 94. 1999. pp. 450-4.

(This was a prospective cohort trial of twin gestations undergoing TVCL at 23 weeks’ gestation. A TVCL of ≤25 mm had a sensitivity of 100%, 80%, and 47% for spontaneous PTB at <28, <30, and <32 weeks respectively.)

Grobman, WA, Gilbert, SA, Iams, JD. "Activity restriction among women with a short cervix". Obstet Gyncol. vol. 121. 2013. pp. 1181-6.

(This was a secondary analysis of a randomized trial of 17 alpha hydroxyprogesterone caproate for prevention of PTB among nulliparous women with a singleton gestation and a cervix <30 mm. The women who were put on any form of activity restriction by their providers actually had a higher risk of PTB <37 weeks [(AOR 2.37; 95% CI 1.60-3.53], even after controlling for potential confounding factors.)

Mozurkewich, BL, Luke, B, Avni, M. "Working conditions and adverse pregnancy outcome: A meta-analysis". ObstetGynecol. vol. 95. 2000. pp. 623-35.

(A meta-analysis inclusive of over 160,000 singleton pregnancies demonstrated high rates of adverse pregnancy outcome in women with physically demanding work. PTB was significantly associated with prolonged standing, shift- and night-work, or a high cumulative work fatigue score [OR 1.22-1.63].)

Crowther, CA, Neilson, JP, Crowther, CA, Hodnett, ED. "Hospitalization for bedrest in multiple pregnancy". Pregnancy and childbirth module. Cochrane Database of Systematic Reviews [updated 3 June 1997]. Cochrane collaboration, Issue 3. Updated software. 1997.

(Four prospective, randomized trials of routine hospitalization of twins were performed. A meta-analysis of their results has not demonstrated a prolongation of pregnancy or any other consistent benefit. Of concern, significantly more twins were VLBW and delivered prior to 34 weeks’ gestation among the hospitalized cohort which resulted in a higher rate of early neonatal demise.)

Romero, R, Nicolaides, K, Conde-Agudelo, A. "Vaginal progesterone in women with an asymptomatic sonographic short cervix in the mid-trimester decreases preterm delivery and neonatal morbidity: A systematic review and meta-analysis of individual patient data". Am J Obstet Gynecol. vol. 206. 2012. pp. 124-39.

(This meta-analysis evaluated the efficacy of vaginal progesterone in several different clinical scenarios. Five prospective randomized trials of vaginal progesterone enrolled multiple gestations, albeit, in limited numbers. The meta-analysis revealed a nonsignificant 30% reduction in the frequency of PTB <33 weeks [RR 0.70; 95% CI 0.34-1.44] and a significant 48% reduction in composition neonatal morbidity/mortality [RR 0.52; 95% CI 0.29-0.93].)

Schuit, E, Stock, S, Rode, L. "for the Global Obstetrics Network (GONet) Collaboration. Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: An individual participant data meta-analysis". British Journal of Obstetrics and Gynecology. vol. 122. 2015. pp. 27-37.

(An individual participant data meta-analysis was performed on all randomized clinical trials of 17 alpha hydroxyprogesterone caproate or vaginally-administered natural progesterone compared with placebo or no treatment, to determine the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies. In unselected women with an uncomplicated twin gestation, treatment with progestogens [either 17 P or vaginal progestogen] did not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of < 25 mm, however, further research is warranted.)

Brizot, ML, Hernandez, W, Liao, AW. "Vaginal progesterone for the prevention of preterm birth in twin gestations: A randomized placebo-controlled, double-blind study". American Journal of Obstetrics and Gynecology. vol. 213. 2015. pp. 82.E1-9.

(This was a prospective, randomized, double-blind, placebo-controlled trial that involved 390 naturally-conceived twin pregnancies with no history of preterm delivery. They were randomly assigned to either daily vaginal progesterone (200 mg) or placebo pills until 34 weeks and 6 days' gestation. In these unselected twin pregnancies, vaginal progesterone administration did not prevent preterm delivery nor did it reduce neonatal morbidity or death.)

Rouse, DJ, Caritis, SN, Peaceman, AM. "A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins". N Engl J Med. vol. 357. 2007. pp. 454-61.

(The NIHMaternal-Fetal Medicine Units Network performed a prospective randomized trial of weekly 17-P injections [250 mg IM or matching placebo] starting at 16-20 weeks of gestation and ending at 35 weeks. The intervention did not reduce the frequency of PTB before 35 weeks [41.5% in the 17-P group vs. 37.3% in the placebo group] nor did it reveal any other benefit in any subgroup analysis.)

Keirse, MJNC, Keirse, MJNC, Renfrew, MJ, Neilson, JP, Crowther, C. "Prophylactic oral betamimetics in twin pregnancies". Pregnancy and childbirth module. Cochrane Pregnancy and Childbirth Database [revised 24 March 1993]. Cochrane Collaboration, Issue 2. Update Software. 1995.

(This meta-analysis of 7 prospective randomized trials failed to demonstrate any consistent beneficial effects on the rates of PTB, birth weight, or neonatal mortality when beta-adrenergic tocolytics was used prophylactically in twin gestations.)

Berghella, V, Odibo, AO, To, MS, Rust, OA. "Cerclage for short cervix on ultrasonography: meta-analysis of trials using individual patient-level data". Obstet Gynecol. vol. 106. 2005. pp. 181-9.

(This meta-analysis includes four prospective trials of twin gestations with a mid-trimester TVCL <25 mm randomized to cerclage placement or not. Cerclage placement in the face of a shortened cervical length did not improve perinatal outcome. In fact, the twins receiving a cerclage had a 2-fold higher risk of PTB [OR 2.15; 95% CI 1.15-4.01].)

Newman, RB, Krombach, RS, Myers, MC. "Effect of cerclage on obstetrical outcome in twin gestations with a shortened cervical length". Am J Obstet Gynecol. vol. 186. 2002. pp. 634-40.

(This prospective observational cohort study was performed and a prophylactic cerclage was offered to all twin gestations with a TVCL <25 mm between 18-24 weeks’ gestation. Cerclage did not improve the length of gestation for those twins with a shortened cervix.)

Roman, A, Rochelson, B, Fox, NS. "Efficacy of ultrasound-indicated cerclage in twin pregnancies". American Journal of obstetrics and gynecology. vol. 212. 2015. pp. 788.E1-E6.

(Thisis a retrospective cohort study of asymptomatic twin pregnancies with a TVCL less than 25 mm at 16-24 weeks’ gestation. One hundred and forty women were managed with either an ultrasound indicated cerclage [n=57] or no cerclage [n=83]. There were no significant demographic differences other than women who underwent cerclage presented at an earlier gestational age and had a shorter cervical length. After adjusting for gestational age at presentation, there were no significant differences in outcome between the two groups. However, in the subgroup, women with a cervical length less than 15 mm [32 with ultrasound indicated cerclage and 39 controls] the interval between diagnosis and delivery was significantly prolonged by approximately 4 weeks, and the incidence of spontaneous PTB <34 weeks was significantly reduced from 80% to 50% in the cerclage group. Admission to the NICU was reduced from 83% [63/76 infants] in the control group to 65.5% [38/58 infants] in the cerclage group.)

Liem, S, Schuit, E, Hegeman, M. "Cervical pessaries for the prevention of preterm birth in women with a multiple pregnancy (ProTwin): a multicentre open-label randomized controlled trial". Lancet. vol. 382. 2013. pp. 1341-49.

(808 twin pregnancies were randomized to receive either an Arabin pessary [n=401] or standard care [n=407]. There was no difference in the rate of composite of poor perinatal outcome in either the pessary [13%] or the standard care control group [14%]. However, in a planned subgroup analysis of those twins with a TVCL <25th percentile, the Arabin pessary reduced composite poor maternal and child outcomes by approximately 60%, and the pessary group had a significantly lower risk of delivery, both before 28 and 32 weeks’ gestation.)

Nicolaides, KH, Syngelaki, A, Poon, LC. "Cervical pessary placement for prevention of preterm birth in unselected twin pregnancies: a randomized controlled trial". American Journal of Obstetrics and Gynecology. vol. 214. 2016. pp. 3.E1-9.

(In this multicenter, randomized, controlled trial, twin pregnancies were randomized to cervical pessary placement between 20 and 24 weeks’ gestation versus expectant management. A total of 1180 women participated; 590 received cervical pessary and 590 were expectantly managed. In women with twin pregnancies, routine treatment with cervical pessary does not reduce either the rate of spontaneous PTB or adverse neonatal outcomes.)

Goya, M, de la Calle, M, Pratcorona, L. "for the PECEP-Twins Trial Group.Cervical pessary to prevent preterm birth in women with twin gestation and sonographic short cervix: a multicenter randomized controlled trial (PECEP-Twins)". American Journal of Obstetrics and Gynecology. vol. 214. 2016. pp. 1 45-52.

(This was a prospective, open-label, multicenter, randomized, clinical trial conducted at five Spanish hospitals. Cervical length of 2287 women was measured of which 137 had a sonographic cervical length <25 mm. These women were randomly assigned to receive a cervical pessary versus expectant management. The insertion of the cervical pessary was associated with a significant reduction in spontaneous PTB less than 34 weeks [16.2% vs. 39.4%]. Pessary use was also associated with a significant reduction in LBW [<2500 gram] deliveries, but no significant differences were observed in composite neonatal morbidity [5.9% vs. 9.1%].)

Fox, NS, Gupta, S, Lam-Rachlin, J. "Cervical pessary and vaginal progesterone in twin pregnancies with a short cervix". Obstetrics and gynecology. vol. 127. 2016. pp. 625-30.

(This was a retrospective cohort study of twin pregnancies managed by a single maternal fetal medicine practice between 2005-2015. All twin gestations with a cervical length <20 mm prior to 28 weeks of gestation were included. All twins received vaginal progesterone. Twenty-one patients received a cervical pessary and they were compared to 63 women in the control group matched for gestational age at diagnosis and cervical length. Patients with a pessary had a significantly lower incidence of delivery <32 weeks of gestation [4.8% vs. 28.6%], a longer interval to delivery by almost 2 weeks, and a lower incidence of severe neonatal morbidity [9.5% vs. 34.9%].)

Grantz, KL, Grewal, J, Albert, PS. "Dichorionic twin trajectories: the NICHD Fetal Growth Studies". American Journal of Obstetrics and Gynecology. 2016.

(One hundred and seventy-one women with dichorionic twin gestations were followed prospectively throughout pregnancy with serial ultrasound studies. Dichorionic twin growth trajectories were established for estimated fetal weight and multiple fetal biometric measurements. The fetal growth trajectories for dichorionic twins were compared with recently developed fetal growth standards established for normal singleton pregnancies. A comparatively asymmetric fetal growth pattern in twin gestations was identified, initially evident at 32 weeks of gestation.)

Burgess, JL, Unal, ER, Nietert, PJ, Newman, RB. "Risk of late preterm stillbirth and neonatal morbidity for monochorionic and dichorionic twins". Am J Obstet Gynecol. vol. 210. 2014. pp. 578.e1-578.e9.

(A retrospective cohort study was performed on 768 twin gestations [601 DC and 167 MC] cared for and delivered at ≥34 weeks of gestation at a single institution. The twins were cared for as part of a longstanding twin clinic with standardized management and fetal surveillance protocols supervised by a consistent maternal-fetal medicine specialist. Using this surveillance strategy the prospective risk of IUFD ≥34 weeks was 0.17% [n=1] for DC twins and 0% for MC twins. Composite neonatal morbidity decreased with each gestational week and the nadir of composite neonatal morbidity occurred at 36/0–36/6 for MC twins and 37/0–37/6 weeks for DC twins.)

Kahn, B, Lumey, LH, Zybert, PA. "Prospective risk of fetal death in singleton, twin, and triplet gestations: implications for practice". Obstet Gynecol. vol. 102. 2003. pp. 685-92.

(This United States population-based analysis from 2003 looked at the intersection between neonatal and fetal mortality rates in twins. The intersection of a falling neonatal mortality rate and a rising stillbirth rate occurred at 38 weeks’ gestation.)

Spong, CY, Mercer, BM, D'alton, M, Kilpatrick, S, Blackwell, S, Saade, G. "Timing of indicated late-preterm and early-term birth". Obstet Gynecol. vol. 118. 2011. pp. 323-333.

(Of all twin births, 50% deliver preterm with 30% delivering in the late-preterm period. Uncomplicated dichorionic twins have optimal outcomes when delivered at 38 weeks’ gestation. Uncomplicated monochorionic twins have a higher risk of stillbirth, thus a late preterm delivery [34-37 weeks] is recommended.)

Newman, RB, Unal, ER. "Multiple gestations: timing of indicated late preterm and early-term births in uncomplicated dichorionic, monochorionic, and monoamniotic twins". Semin Perinatol. vol. 35. 2011. pp. 277-85.

(This is a review of multiple, population-based, retrospective, and prospective cohort trials. These studies suggest that delivery of an uncomplicated dichorionic twins at 38 weeks’ gestation is associated with the lowest rate of stillbirth and neonatal mortality, as well as neonatal morbidity and hospital costs.)

Barrett, JFR, Hannah, ME, Hutton, EK. "A Randomized Trial of Planned Cesarean or Vaginal Delivery for Twin Pregnancy". N Engl J Med. vol. 369. 2013. pp. 1295-305.

(A prospective randomized trial was performed involving twin pregnancies with the first twin in a cephalic presentation to either planned cesarean or planned vaginal delivery. Enrollment occurred between 32 weeks 0 days and 38 weeks 6 days. A total of 1398 women [2795 fetuses] were randomly assigned to planned cesarean delivery and 1406 women [2812 fetuses] to planned vaginal delivery. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity. There was no significant difference in the composite primary outcome between the planned cesarean group [2.2%] and the planned vaginal delivery group [1.9%; OR 1.16; 95% CI 0.77-1.74]. These findings remained true regardless of presentation [cephalic/cephalic vs. cephalic/non-cephalic or chorionicity].)

Hutton, EK, Hannah, ME, Ross, S. "Maternal outcomes at 3 months after planned cesarean section versus planned vaginal birth for twin pregnancies in the Twin Birth Study: A randomized controlled trial". British Journal of Obstetrics and Gynecology. vol. 122. 2015. pp. 16 53-62.

(Women enrolled in the original Twin Birth Study were invited to complete a series of questionnaires 3 months following delivery. Two thousand, five hundred and seventy women (92% response rate) participated in the study. No significant differences in outcome at 3 months were identified. Mode of birth was not associated with urinary incontinence, quality of life, fatigue, or postpartum depression. Contrary to previous studies, breastfeeding at 3 months was not increased with planned a vaginal birth. Outcomes were evaluated based on intent to treat.)

Asztalos, EV, Hannah, ME, Hutton, EK. "Twin Birth Study: 2-year neurodevelopmental follow-up of the randomized trial of planned cesarean or planned vaginal delivery for twin pregnancy". American Journal of Obstetrics and Gynecology. vol. 214. 2016. pp. 371.e1-19.

(A total of 4603 children from the initial cohort of 5565 fetuses/infants (83%) were screened using the Ages and Stages questionnaire and by clinical neurodevelopmental assessment at 2 years of age. Baseline maternal, pregnancy, and infant characteristics were similar. There was no significant difference in the outcome of death or neurodevelopmental delay: 5.99% in the planned cesarean versus 5.83% in the planned vaginal delivery groups. Randomization in the original study included uncomplicated twin gestations between 32-0/7 and 38-6/7 weeks' gestation where the first twin was in a cephalic presentation.)

Newman, RB, Ellings, JM. "Antepartum management of the multiple gestation: the case for specialized care". Semin Perinatol. vol. 19. 1995. pp. 387-403.

(The establishment of a specialized, multidisciplinary twins clinic was associated with significant reductions in preterm PROM, VLBW delivery, and perinatal mortality compared to historic and contemporary controls.)
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