Learn everything you ever wanted to know about prenatal genetic testing by downloading my ebook!

Who needs prenatal testing for genetic disorders? How much does your risk of carrying a baby with a genetic disorder increase with your age? Which prenatal test or screen is right for you?

These are among the questions my amazing co-author Molly Dickens (and fellow pregnant scientist blogger/partner-in-crime) and I tackle in our new ebook on prenatal testing. We provide a quick “cheat sheet” on how these tests compare, and then dig into the nitty-gritty details of each as well as the history of prenatal testing and how to estimate your personal risk of carrying a baby with a genetic disorder.

Even having gone through prenatal testing twice before, I was still surprised to learn while researching this book that…

  1. Testing only women over 35, as was the case in the 80s and early 90s, misses around 70% of the cases of Down’s Syndrome.
  2. The risk of miscarriage from amnio and CVS is around 1 in 1000–far, far lower than the still commonly cited but outdated 1 in 100 estimate.
  3. Until you are 38 years old, you are more likely to carry a baby with a chromosomal disorders involving tiny pieces of chromosomes than carry a baby with disorder involving missing or extra whole chromosomes–but these disorders are not well detected by any prenatal screens. This is a huge problem, because younger women are often advised to get screens over diagnostic testing.
  4. How women under 35 are more than twice as likely to get a false alarms on prenatal screens as women over 35.

And so much more that I am excited to share.

We all need to up-to-date, evidence-based information to make the best decisions for us and our families. But with prenatal testing rapidly evolving, sometimes doctors and other healthcare professionals are woefully behind or outright misinformed on the latest developments. So please download and share with fellow parents-to-be!

Download the pdf here: Prenatal Testing ebook.

Light Drinking During Pregnancy: 7 Things You Need to Know

Last year, the CDC ignited a firestorm of criticism by stating that women should “stop drinking alcohol if they are trying to get pregnant or could get pregnant”, and–because an estimated 50% of pregnancies in the U.S. are unplanned–any woman who drinks alcohol should use birth control.

“Its [the CDC’s] underlying message was unmistakable: Women should consider themselves first a vessel for human life and make decisions about their health and behavior based on that possibility,” Rebecca Ruiz wrote at Mashable, in a typical reaction.

The (completely understandable) outrage at the CDC’s tone-deaf and condescending messaging has, unfortunately, drowned out information on the key question for many pregnant women: Is any amount of alcohol during pregnancy okay? And are there times when it should be absolutely avoided?

We all know that heavy drinking and binge drinking are harmful during pregnancy. Fetal alcohol syndrome, caused by heavy drinking during pregnancy, affects an estimated 2 to 7 children out of 1000. Another 2 to 7% of U.S. children are thought to suffer milder forms of cognitive impairment due to alcohol exposure in the womb.

But what about light drinking, a champagne toast or an occasional glass of wine at dinner? Women–pregnant, pre-pregnant, and otherwise–receive conflicting advice about the safety of light drinking.

Economist Emily Oster, in her bestselling pregnancy advice book Expecting Better, says pregnant women can be comfortable with “1 to 2 drinks a week in the first trimester” and one drink daily afterward, a stance she continues to stand behind.

Many doctors also greenlight the occasional drink, as Ruth Graham of Slate notes: “Many doctors seem perfectly comfortable with moderate alcohol consumption in the late stages of pregnancy. When I told my doctor that I was enjoying a glass of wine per week in my third trimester, she didn’t bat an eye.”

The CDC, on the other hand, maintains that no amount of drinking is safe.

“Any drinking is going to put your child at risk,” according to Clark Denny, a CDC epidemiologist. “You should not drink if you are pregnant, are considering getting pregnant or even if you could possibly get pregnant.”

Other countries, like the U.K. and France, that once gave less stringent advice–pregnant women should not exceed 1-2 drinks per week–now state no amount of drinking is safe, and that women who are pregnant or trying to conceive should abstain entirely.

At the heart of this debate is the research itself. So, what do we actually know about light drinking during pregnancy?

Let’s start with alcohol and the risk of miscarriage.

  1. Light drinking, the equivalent of 1-2 drinks per week, during the first trimester, boosts the odds of a first trimester miscarriage by about 30%, and the odds of a early second trimester miscarriage (between 13-16 weeks) by about 70%, according to a large study of over 90,000 pregnancies in Denmark. The risk rose with greater intakes. Drinking 4 or more drinks per week during the first trimester more than doubled the odds of a miscarriage. A U.S. based study found that women who drink 2 times per week in their first trimesters had a 25% chance of miscarriage, compared to a 14% chance for those who abstained. Other studies also find a higher risk of miscarriage for light drinkers (see here and here).

Does this mean that light drinking early in pregnancy causes miscarriage? Unfortunately, we cannot say for sure. Experimental studies in humans are impossible, so there are a lot of unknowns.

For one, some women may understate how much they actually drank during pregnancy, so the apparent rise in miscarriage could actually stem from moderate to heavy, rather than light, drinking.

Women who drink heavily during pregnancy often also smoke or have partners who smoke, and are more likely use drugs, receive worse prenatal care, live in poverty and experience extreme chronic stress–all of which can raise the risk of miscarriage and cognitive problems in their children, and any and all of these factors could exacerbate the toxic effects of alcohol on the fetus.

Poor nutrition and smoking in particular seem to worsen the effects of alcohol; alcohol lowers the amount of nourishment reaching the fetus.

Women who drink alcohol during their first trimester may have less nausea. (I for one could not get near alcohol in my first trimester, as much as I might, after a long day of nausea and chasing after a toddler, desire a drink.) Although about 25% of women do not experience nausea during pregnancy, an absence of nausea is linked with an increased risk of miscarriage, probably because poorly developing pregnancies produce fewer symptoms.

And finally, the problem may not arise from drinking during early pregnancy but from drinking before pregnancy.

2. Drinking alcohol may lower the chances of pregnancy, and increase the chances of miscarriage, by causing chromosomal abnormalities in the egg before ovulation. Alcohol has been shown to impair meiosis, the critical two-step cell division in maturing egg follicles, leading to chromosomally abnormal eggs. Chromosomal abnormalities account for over half of first trimester miscarriages. Worse, because eggs take several months to fully mature, even drinking in the months before conception could be harmful.

How much alcohol do you have to drink to harm your eggs? Again, we don’t have a good answer. The degree of harm likely depends on a lot of other things, like your age, your overall fecundity, your alcohol tolerance, how much alcohol you drink, and when you drink relative to critical phases in the egg’s development.

Clearly, even formerly heavy drinkers go on to have chromosomally normal and perfectly healthy pregnancies, so the effect is not absolute. The increase in chromosomal abnormalities is probably most problematic for couples already suffering from fertility issues. Among couples undergoing IVF, for instance, drinking appears to lower their chances of pregnancy.

Because the human data are limited, we have to turn to animal models. In one study using monkeys, the equivalent of binge drinking (4-5 drinks at a sitting) twice a week lowered the number of chromosomally normal eggs and increased the chances of miscarriage.

3. Alcohol does not reach the developing embryo until the 3rd week after fertilization, or pregnancy week 4, right after most pregnancy tests turn positive. In other words, even if you got pregnant on your honeymoon while more than a little tipsy and drank cocktails on the beach for the rest of the week, you have nothing to worry about. That alcohol did not reach your embryo.

What about harm to the fetus’s developing brain? Here’s the problem: No one knows at what threshold drinking alcohol becomes harmful, and that threshold may vary from person to person, just like alcohol tolerance and metabolism varies from person to person.

Heavy drinking and frequent binge drinking are clearly bad, but what about that occasional glass of wine or cocktail?

Emily Oster finds the not one drop rule propounded by the CDC and others absurd, and it’s easy to see where she is coming from. Lots of chemicals known to be harmful in large quantities are completely safe in small amounts. As she puts it,

“If you have too many bananas (and I mean a LOT of bananas), the excess of potassium can be a real problem, but no doctor is going around saying “No amount of bananas have been proven safe!” He’d be laughed out of a medical conference.”

But this argument, a version of the Paracelsus principle–the dose makes the poison–depends on the poison in question. Some toxins, like lead, are considered unsafe at any amount.

We don’t have great information about the actual threshold at which alcohol causes harm, or when harm is most likely to occur. But let’s sift through what we do know.

4. By the third week after conception (the 5th week of pregnancy), alcohol and its byproducts cross the placenta. Based on animal research, the fetus is believed to experience the same blood alcohol level as its mother.

5. Alcohol is a known neurotoxin. Although how alcohol causes damage is not entirely clear, neuronal loss with heavy or binge drinking is evident in animals and in humans. Harmful effects may be especially pronounced in the developing brain, particularly during the first trimester, when many of the changes in facial morphology in FAS appear to originate. Damage to slow growing brain structures, like the cerebellum, likely occurs throughout pregnancy.

6. Large epidemiological studies find no evidence of cognitive impairment with light drinking (1-2 drinks per week) in the second and third trimesters and less than a drink a week, on average, in the first trimester. This research is the basis of Emily Oster’s claim that a drink a day in the second and third trimesters is okay.

One of the largest of these studies is the U.K. Millennium cohort, which has followed a nationally representative sample of 11,000 children born betwen 2000-2002. At age 3, age 5, and age 7, both boys and girls whose mothers drank about 1-2 drinks per week actually had better overall cognitive performance and fewer behavioral and attention problems than children whose mothers abstained from drinking during pregnancy. Heavier drinking, on the other hand, was associated with worse cognitive performance and more behavioral problems.

(The higher test scores among children of light drinkers was almost surely NOT because alcohol benefited their development, but because women who drank lightly were on average more educated and of a higher socioeconomic status than women who abstained. This confounding of light drinking with education and socioeconomic status is actually a huge problem for interpreting this study’s results. Parental education, income, and social class all predict better cognitive performance and fewer behavior problems. So, who is to say that these children would not have been more advantaged had their mothers abstained throughout pregnancy?)

Other studies have found no effect on test scores or mental health at age 11 among children of mothers who drank less than 1 glass per week during their first trimester; no increase in mental health or behavior problems among children of light drinkers at age 2, 5, and 8 (but worse mental health seen among moderate, binge, and heavy drinkers); and no impairment in cognition, learning, or attention among 14 year olds whose mothers drank an average of less than a glass a day early or late in pregnancy; and no reduction in IQ, attention, or executive function at age 5 in women who drank up to an average of 5 drinks per week.

In short, light drinking during pregnancy, less than a drink a day on average, and no more than 1 drink at a sitting, has not been shown to cause detectable harm.

Because light drinking is more common among highly educated, high income women, the advantages of which could mask any subtle impairments caused by small doses of alcohol, we need to take these findings with a grain of salt.

7. Individual differences in alcohol metabolism and clearance probably determine the threshold at which alcohol causes harm. This is clear even among heavy drinkers: Only about 5% of babies born to women who abuse alcohol during pregnancy suffer from FAS.

But a recent study looking at IQ at age 8 found that among women who were genetically poor alcohol metabolizers, moderate drinking (1-6 drinks/week) was associated with lower IQ. Children of fast alcohol metabolizers, on the other hand, did not have lower IQs on average, nor did children of among poor metabolizers who abstained from drinking during pregnancy.

The Bottom Line

Drinking more than 2 drinks a week in the first trimester appears to substantially increase the risk of miscarriage. That said, we do not know whether alcohol causes miscarriage. A lack of nausea, or other problems that often go along with alcohol, like smoking, may contribute to or fully explain this effect.

One possible reason is that alcohol can cause chromosomal abnormalities in the egg prior to conception. Alcohol use before conception does NOT preclude a healthy pregnancy (clearly!). Still, couples who are struggling to conceive may boost their chances by abstaining from alcohol.

What about children’s cognitive abilities and emotional and mental health? Here, very light drinking, less than a drink per week on average, has not been not been shown to be harmful. And many studies find no harmful effects of 1-2 drinks per week.

However, women vary considerably in their ability to metabolize alcohol, based on their body size, liver size, and genetics. Other factors, like whether you drink with food and how quickly you drink (no tequila shots, please!), also affect the amount of alcohol reaching the fetus. So setting a “safe” threshold is basically impossible.

Given this variability, here’s my personal take: It seems wise to largely avoid alcohol during pregnancy, especially during the first trimester. An occasional glass of wine drunk slowly with dinner is probably fine, but I personally don’t see the upside to pushing the limits.

At the same time, women who drank a glass of wine here and there have no cause for alarm. The CDC’s draconian, not-one-drop stance is probably based on a slippery slope argument. If they say an occasional glass of wine or beer is fine, then some women might read this as license to overindulge.

On the other hand, Emily Oster’s advice to drink “up to 1 drink a day in the second and third trimesters, and 1 to 2 drinks a week in the first trimester” feels too risky for my blood. Most studies define light drinking as 1-2 drinks per week, much lower than Oster’s recommended maximum for the second and third trimesters.

Naturally, every woman is going to weigh the risks and benefits of light drinking a little differently. A reasonable woman could see the available evidence and feel comfortable with 1 to 2 drinks a week; another reasonable woman could see the available evidence and decide to abstain entirely.

What about drinking after pregnancy? Check out my post on drinking while breastfeeding.

No, C-sections Are Not “Best With a Little Labor”

Children born by C-sections have about 20% higher odds of obesity, asthma, allergies, and Type 1 Diabetes, according several large research reviews.

But are children born by scheduled C-sections especially at risk for health problems, as a recent New York Times piece claims?

“the data showed more health problems among babies born by planned C-section than among those delivered by emergency C-section or vaginal birth, even though the planned surgery is done under more controlled conditions. The finding suggests that the arduous experience of labor — that exhausting, sweaty, utterly unpredictable yet often strangely exhilarating process — may give children a healthy start, even when it’s interrupted by a surgical birth.”

A reader, confused by this New York Times piece, wrote to ask for my take. “Are planned C-sections really less safe?” she asked. “The actual study… didn’t seem to support what the NYTimes article claimed.”

And after reviewing the research myself, I have to agree.

The study in question, led by Dr. Mairead Black of the University of Aberdeen, and one of the largest and best-designed studies on long-term health following delivery by C-section, actually did not find more health problems among children born by planned C-sections than those born by emergency C-sections.

(The sole exception was an unexpected–and probably artifactual–increase in Type 1 Diabetes; more on this in a moment).

How Does This Study Fit in With What We Already Know?

Although C-sections have been consistently linked with poorer long-term health in children, scientists are still not sure why.

One possibility is babies miss out on the “sweaty and exhausting” experience of labor. The physical trauma of birth kickstarts the baby’s internal stress response, pumping cortisol through their veins, and giving their organs, including the lungs, the final push to full maturity.

Another possibility, favored by many scientists, is that C-sections alter the baby’s gut microbiome. C-section  babies miss out on the messy, bacteria-laden, splash into every bodily fluid passage through the birth canal–the route by which nature normally seeds a baby’s gut microbiome.

“If a baby is born naturally, it comes into contact with bacteria from the mother, which might help with immune system development,” lead researcher Dr. Mairead Black told The New York Times.

Compared to babies born by C-section, babies born vaginally have a more diverse and healthy gut microbiome–believed to be critical for their development of a healthy, balanced immune system (one good at attacking pathogens, but not overly jumpy and prone to self-attack).

Or perhaps the issue is not C-section birth per se, but the hodgepodge of pregnancy and birth complications that often result in C-sections, such as stalled labor, intrauterine growth restriction, and preterm birth.

To study one piece of this puzzle, the importance of labor-induced fetal stress, Black and colleagues at the University of Aberdeen in the UK compared babies born by planned versus emergency C-sections. Babies born by planned C-sections experience no labor, while babies born by emergency C-section often experience some, even though it is cut short.

Black and colleagues followed over 300,000 full-term singleton babies born to first-time mothers in Scotland between the years 1993 and 2007. Roughly 4% were born by planned C-sections, and 17% by emergency C-sections.

Compared to children born by emergency C-sections, babies born by emergency C-sections were at no higher risk of virtually every health outcome Black and colleagues assessed–asthma, inflammatory bowel disease, obesity at age 5, cancer, or all-cause mortality. In fact, these children born by planned C-section had a wee bit lower risk of dying during their first year of life.

The one exception: Children born by planned C-section appeared to have 50% higher risk of developing Type 1 Diabetes. (A 50% higher risk sounds scary, but because Type 1 Diabetes is rare, this amounts to only 2 additional diagnoses for every 1000 children.)

As the researchers acknowledge, the apparent increase in Type 1 Diabetes was probably not caused by birth by planned C-section, but by some artifact of their study’s design, a third factor not adequately accounted for in their research.

Why did they think this effect was not real? Because children born by planned C-section were not at higher risk of Type 1 Diabetes compared to children born vaginally, a pattern of results inconsistent with prior research, and one which makes little sense. If anything, the researchers expected the opposite, planned C-sections would lower the risk of Type 1 Diabetes. Earlier research has found severe fetal distress stress during labor–something obviously more common during emergency C-sections than during planned ones–raises the risk of Type 1 Diabetes.

My guess? The researchers were unable to completely account for maternal Type 1 Diabetes. Having a mother with Type 1 boosts a child’s chances of Type 1 Diabetes by about 10-fold. (Black and colleagues did try to control statistically for maternal Type 1 Diabetes, but were missing this information for some of the mothers.) To avoid complications during labor, many women with Type 1 Diabetes deliver by planned C-section.

C-sections Versus Vaginal Births

How did the children born by C-section fare compare to those born vaginally?

Overall, children born by C-section, planned or emergency, were more likely to be hospitalized for asthma and had higher mortality rates during the first year of life as well as throughout childhood.

Contrary to earlier research, though, children born by C-section were no more likely to develop inflammatory bowel disease, Type 1 Diabetes, obesity, or cancer.

The Bottom Line

The NYT headline is misleading: Planned C-sections do not lead to worse health outcomes than emergency ones.

The one exception: children born via planned C-sections had a 50% higher risk of Type 1 Diabetes, but only compared with unplanned C-sections. No difference was seen when comparing children born by planned C-section with those born vaginally, a pattern of results which, as the researchers themselves acknowledge, does not make any sense. In fact, this pattern runs counter to prior research, which suggests severe fetal distress during labor ups the odds of Type 1 Diabetes, and a recent meta-analysis which found that C-sections of all types up the odds of Type 1 Diabetes by about 20%.

Why is birth by C-section associated with poorer health? We still do not know. Given the impossibility of randomized controlled trials for childbirth, we may never know.

But this study does have one take-away: missing out on labor-driven stress response is probably not the critical issue. If it were, we would see significantly worse health outcomes among children of planned C-sections than emergency C-sections.

As for the risks of C-sections overall, that’s too big of a topic for me to tackle here. But I will say this: C-section-driven health risks are minor. They are almost certainly swamped out by who we are–the genetic blessings and curses we bestow on our offspring–and what we do as parents.

(Not reassured? You can always swab your C-section-born baby’s skin and mouth with your vaginal secretions, as widely-respected gut microbiome researcher Rob Knight did after his wife’s emergency C-section. I certainly would.)

 

Folic Acid During Early Pregnancy May Lower the Risk of Autism

We all know that taking folic acid before and during early pregnancy helps prevent neural tube defects like spina bifida and anencephaly. But I for one was surprised to learn that taking folic acid may also help prevent autism.

Continue reading “Folic Acid During Early Pregnancy May Lower the Risk of Autism”

Back Sleeping During Pregnancy and the Sydney Stillbirth Study

Pregnancy can be cruel. Just when you are at your most swollen, bloated, and exhausted, sleep proves frustratingly elusive. Every night, you toss and turn, trying to find a comfortable position, your back aching, and your belly pressing down on your bladder. And then, as you finally start to drift off, you realize you need to pee.

To make matters worse, despite having an enormous bowling ball attached to your stomach, you are told you cannot sleep on your back:

“After 16 weeks of pregnancy, experts advise women to not sleep on their backs, but rather should lie on their sides, ideally the left side.” – mamalette

Who came up with this idea?

This advice stems three studies that have linked back sleeping with late stillbirth (pregnancy loss after 28 weeks). (Interestingly these warnings predated the three studies, so they are not exactly the reason women are told to avoid back sleeping)

I described the first two studies, one conducted in Ghana, the other in New Zealand, in an earlier post, and concluded that not only did they provide no reason for alarm, they certainly do not justify blanket advice again back sleeping.

In 2015, a third study came out linking back sleeping with late stillbirth. Does it change the overall picture?

Continue reading “Back Sleeping During Pregnancy and the Sydney Stillbirth Study”

Blood-Based Tests of Fetal Sex: Are They Accurate?

Many expectant parents are impatient to learn if they are having a boy or a girl. So they may be attracted to new companies, like SneakPeek, which claim to be able to determine your baby’s sex with 99% accuracy early in the first trimester, with only a simple blood draw.

These new tests rely on what is known as cell free fetal DNA (cffDNA)–small fragments of DNA shed from the placenta into your bloodstream.

Unfortunately, according to a 2011 meta-analysis published in JAMA, some of these companies overstate the accuracy of their tests. The meta-analysis found that none of these cfDNA-based tests are accurate before 7 weeks. (The meta-analysis also examined urine-based tests. None of these were accurate.)

Between 7 and 20 weeks, accuracy for these blood-based tests ranged from 95-98%, depending on the specific techniques employed and the baby’s actual sex. (The tests were more accurate when they use a DNA amplification technique known as real-time quantitative polymerase chain reaction.) Only after 20 weeks were the blood-based tests 97-99% accurate.

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Vitamin D in Breastmilk and My Daughter’s Diagnosis with Type 1 Diabetes

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Sydney, catching bubbles at her birthday party this month.

A few weeks ago, I was all set to write about the vitamin D needs of pregnant and nursing women. Increased sunscreen use and less time spent outdoors means that few women can meet their vitamin D needs through sunlight exposure alone. As a result, many pregnant women are insufficient in the vitamin.

The medical community is clearly concerned about women’s low levels of vitamin D: The American Pregnancy Association recently raised their recommended vitamin D intake for pregnant and nursing women from 400 IU to 4000 IU, a tenfold increase. The change was precipitated by a recent randomized control trial, in which supplementation with 4,000 IUs a day was shown to be safe and highly effective at reducing vitamin D deficiency among pregnant women.

I only wish these changes had come sooner.

I say this because last weekend, my daughter Sydney, who turned two this month, was diagnosed with Type 1 Diabetes–a disease that may be staved off, in part, by high levels of vitamin D during infancy.

Continue reading “Vitamin D in Breastmilk and My Daughter’s Diagnosis with Type 1 Diabetes”