Wednesday, September 30, 2015

Twins of Different Seasons

Biology concepts – twins, dizygotic, delayed interval delivery, steroid hormones, lung development, time of birth

Leonardo DiCaprio starred as the twins Louis and Philipe in
the latest iteration of The Man In The Iron Mask. I’m partial
to Gabriel Byrne, Gerard Depardieu and Jeremy Irons as the
three musketeers. Louis and Philipe were monozygotic
twins, and they are more often born in close proximity,
but not always.
Dateline Monaco, December, 2014 - Princess Charlene and Prince Albert announce the birth of royal twins. The girl, Gabriella, arrived two minutes before the boy, crown prince Jacques Honore. Gabriella is the older, but Jacques is the heir and will inherit about 1 billion dollars. This is according to a state constitution that dates to the 1600’s.

This isn’t the first time twins have thrown a cog in the works of succession. Consider the case of The Man In The Iron Mask. Alexandre Dumas gives us a story of intrigue, murder, revenge and affairs of state in 17th century France. King Louis XIV isn’t the ruler that France deserves, but he’s the one in power and he is cruel.

The musketeers obey him, but begrudgingly. When it comes to be known in the halls of the palace that a young man in the country looks just like the king, we learn that Louis XIV is a twin. The prior king had sent the younger twin (by minutes) to the country to avoid the problems of succession. Louis XIV finds him, imprisons him and forces him to wear the iron mask.

Needless to say, everything turns out just fine. Philipe, the younger twin replaces Louis on the throne with the help of the musketeers and saves the populace from starvation. So, yes, in the end it seems that twins can be a bother on succession.

The real story of the iron mask most likely includes an older brother, not a twin. No one really knows who he was, but he was a prisoner of Louis XIV and was hidden behind a mask. He died in 1703, and his treatment while in prison suggests that he was a royal. Hence, the idea that he may have been a brother of the king.

This is the birth of a baby orca at Sea World in San Diego
last year. When is the baby born? Some people say it’s when
the baby takes its first breath. This is tough to judge for a
whale; it is born underwater, but it has to breathe air. The
first thing mom does is lead baby to the surface. So, the
most common determination is when the whole body
is outside mama. 
Such is the mess that a few minutes can make. If the other baby had pushed his way in front, the king would have been different all along. A few ticks of the clock make all the difference in twins. But how long can the gap be? Let’s continue our discussion of what makes twins more than just siblings. Last week we discovered that "race" isn’t a barrier to twindom – but how long apart can two babies be born and still be considered twins?

The first thing to consider is what defines time of birth. Because certain actions, like delivering the body after the head is out, or cutting the umbilicus after delivery can be delayed by complications, time of birth is usually defined as when the complete body hits the air. For a natural birth, this means a decent time gap between twins. They’re coming down a one lane road and there’s no room to pass or drive side by side. In C-sections, it’s almost always just a minute or two difference, but with natural delivery the average is 17 minutes.

If that time gap comes at the right moment, twins can be born with different birthdates. How many twins this affects in the US is low – and here’s why. About 98% of US births take place in the hospital, and this is probably higher for twins because the risks during delivery are higher.

Hospitals like to deliver babies when it is more convenient for doctors and staff, so they induce labor plan caesarian section births for day time. Therefore, the hours of the day when most babies are born in the United States are between 8:00 am and 9:00 am and between noon and 1:00 pm.

Most mammals are born during the inactive period for
their species – diurnal animas are born at night and
nocturnal animals are most often born in the day. Pigs, for
example are born in the nighttime, so are horses – just
ask any veterinarian.
But, if you have your baby at home, or somewhere other than the hospital, the most likely time is in the wee hours of the night - between 12:00 am and 4:00 am. Evolution may play a role here, a history of nomadic movement meant that mom and baby might be left behind during a daytime delivery, but nights were a time to hide and protect each other – a better time to deliver a baby.

The time of midnight is an artificial construct, made by man to order his day, so having one twin born on the left of midnight and the other born on the right side doesn’t really make a difference. Their birthdays differ by one digit and mom and dad might feel compelled to plan two different parties, but that’s about it.

Likewise, if the twins are born across a midnight that occurs on the last day of a month, then twins could be born in different months – astrologists might consider this important, but I don’t know who else would. Your accountant might point out that if the two children were born across the midnight hour on December 31st, then you’ll get the tax exemption on just one of your two kids for that first year. OK, now I’m listening.

Aaron and Luke Hegenberger were born on the night of December 31st, 1999. Aaron was born at 11:53 pm, while Luke was born just a few seconds after midnight. So, even though they entered the world separated by only eight minutes, the boys were born on different days of different months of different years of two different millennia!

Twins born by C-section have shorter gaps between births
for obvious reason. The short time to second birth is
important, as second twins do better with shorter gaps.  One
study showed how much more stressed the second
twins are while another discussed the idea that
C-section is suggested if the time between births is getting
low, even though C-section has its own risks.
In general, if the babies are near full term, a short birth interval is better, but there can be times when leaving one bun in the oven is advisable. With the use of more assisted reproductive therapies like in vitro fertilization, there are more twins being born, but also more problems – twin births always have more chance for problems.

There can be growth discordance, where one fetus just matures faster than the other. Delivering twin A might be warranted, but twin B could use another few days of maturation. This brings us to the idea of delayed interval delivery (DID) of multiples. Medical professionals now have ways to deliver one baby and delay the birth of the second.

It is a sad thing to contemplate, but twin pregnancies are associated with higher rates of miscarriage. When one twin dies in utero and must be delivered, all efforts are made to save the second twin. This would include delaying its delivery until it is past the 25th week. Just a few days can make all the difference.

The lungs are the primary concern when delivering preterm infants. At about 25 weeks of gestation, the lungs begin to change morphology. They go from the canalicular stage (tubal) to the saccular stage, meaning they start to develop alveoli, the air exchanging sacs of the lung.

Retinopathy of prematurity is caused by using high tension
oxygen with preemies. The high pressure oxygen helps with
immature lungs, but it causes overgrowth of blood vessels
in the retina and can lead to complete blindness. This
occurred a lot in the 1960’s before they realized the risks.
At this same time, the lungs start to produce surfactant, a phospholipid and protein concoction that allows better gas exchange across the fluid/air interface by reducing the surface tension of the lung tissue. Surfactant also keeps the lung surfaces from sticking to one another during exhalation so that inhalation is easier.

Many studies have shown that if one twin is delivered before 25 weeks, there is a lower chance of survival. Delaying the second twin’s delivery is met with a much improved prognosis. One study indicated that in one health center, 25% of first twins born between 15-25 weeks of gestation survived, but delaying the second delivery to 25-31 weeks improved the survival of the second twin to 75% percent.

A six year study in a different birthing center showed a 14.3% survival for 22-25 week first twins, but delaying the birth of the second twin by just nine days on average improved their survival to 57.1%. This is astonishing.

I can think of two main issues when delaying birth of the second twin; 1) how to stop the second twin from coming out, and 2) how to make the most of the delay time. Both are critical and both can be managed in some cases.

Oxytocin is the hormone that induces labor contractions. They
are described as wave-like. They start at the top and contract
down the sides of the uterus. This forces the baby’s head
toward the birth canal.
To delay the second delivery, doctors can give tocolytic (toco from Greek = childbirth and lysis = release or dissolve) drugs. These compounds, like Nifedipine and Terbutaline, work to suppress labor. That means that they relax the uterine walls and counteract the body’s hormone (oxytocin) induced reaction to create contractions and push the baby out. But there are other ways as well.

Doctors can close the birth canal with sutures (called cervical cerclage); this often has the same effect on contraction production, or they can use an endometrial loop.

But the main issue is to get the second baby’s lungs to mature so that they can survive on the outside. You could just wait as long a possible to deliver the second baby, but giving them a push is better. Antenatal corticosteroids (ante = before and natal = birth) corticosteroids are a way to help out.

Baby Stewie from Family Guy got into some steroids and bulked
up in one episode. These steroids are different from the
glucocorticoids used to induce lung maturation. Stewie took
anabolic steroids, but both are lipid and have receptors inside
the cells, not on the surface. Warning, steroids DO NOT give you
big muscles, they just let you recover faster, so you can work
harder to get big muscles – and they cause major health problems.
Glucocorticoids like cortisone induce a quicker maturation of the lungs. Steroids are often associated with differentiation of cells, and here it proves mighty helpful. The steroids are lipids, so they travel right through the cell membrane. Their receptors are located in the nucleus and control the expression of genes – steroids change mRNA production levels for certain genes. In the lungs, it is the genes that help the cell differentiate into mature lung cell types and to make surfactant.

Just a few days of steroids will significantly improve the outcomes of premature births, and all of these techniques together allow for some amazing delays in twin delivery. The record? Well, the longest ones I could find in the literature were 104 days in one case and 101 days in another (that's 3.5 months!) – these were with cervical cerclage and tocolytic treatment. But it also occurs in natural deliveries. A 2012 case in Ireland occurred where the contractions just stopped after the delivery of a first premature twin. Eighty seven days later her sister was born.  So – do we still define twins as babies born about the same time?

Next week – let’s shatter the last of the twins definitions. Do they have to come from the same father? Do they have to be conceived at the same time? No and no.

Reinhard, J., Reichenbach, L., Ernst, T., Reitter, A., Antwerpen, I., Herrmann, E., Schlösser, R., & Louwen, F. (2012). Delayed interval delivery in twin and triplet pregnancies: 6 years of experience in one perinatal center Journal of Perinatal Medicine, 40 (5) DOI: 10.1515/jpm-2011-0267

Padilla-Iserte, P., Vila-Vives, J., Ferri, B., Gómez-Portero, R., Diago, V., & Perales-Marín, A. (2014). Delayed Interval Delivery of the Second Twin: Obstetric Management, Neonatal Outcomes, and 2-Year Follow-Up The Journal of Obstetrics and Gynecology of India, 64 (5), 344-348 DOI: 10.1007/s13224-014-0544-1

Lewi, L., Devlieger, R., De Catte, L., & Deprest, J. (2014). Growth discordance Best Practice & Research Clinical Obstetrics & Gynaecology, 28 (2), 295-303 DOI: 10.1016/j.bpobgyn.2013.12.003

Hjortø, S., Nickelsen, C., Petersen, J., & Secher, N. (2014). The effect of chorionicity and twin-to-twin delivery time interval on short-term outcome of the second twin Journal of Maternal-Fetal and Neonatal Medicine, 27 (1), 42-47 DOI: 10.3109/14767058.2013.799657

For more information or classroom activities, see:

Delayed interval delivery -