If you’ve tested positive with a home pregnancy test, give us a call. We will schedule an appointment for you approximately eight weeks from your last menstrual period.
During pregnancy you should avoid fish that contains Mercury (including swordfish, tile fish, mackerel and shark). Also avoid saccharine, alcohol, deli meats, unpasteurized cheeses, and meat, poultry and fish that have been under-cooked.
For most women, there is no medical reason not to have sex during pregnancy. Unless your pregnancy is classified as high risk or if there are other safety concerns, you and your partner can have sex without fear of harming your baby.
It is safe to exercise in moderation during pregnancy, unless your obstetrician advises against it. Some exercises can help with childbirth.
It is usually safe to travel by airplane up to 35 weeks into your pregnancy. If you need to travel after 35 weeks, check with your physician. To reduce your chances of getting a blood clot during a flight, get up to stretch your legs several times.
Prenatal vitamins, which are now available without a prescription, are safe to take during pregnancy. For any other medications, vitamins, herbal remedies or supplements, check with your physician.
If you are pregnant and you get a cold, check with your physician before taking any over-the-counter cold or cough medications, especially if they contain aspirin or ibuprofen. In most cases, it is safe to take Tylenol (acetaminophen) for minor aches and pains. Saline nasal sprays or steam inhalation may help with congestion. Remember to drink lots of fluids.
We recommend that you get a flu shot if you are pregnant during flu season. It’s safe to get a flu shot even if you are in the first trimester.
Most pregnant women experience no serious complications if they are exposed to the Fifth disease virus. However, anemia or miscarriage is possible, especially in the early stages of pregnancy. If you suspect or know you’ve been exposed to the Fifth disease virus, contact your health care provider. If you have the virus, your physician may decide to monitor you more closely.
Since very little of the chemicals in hair dye are absorbed into your system, it’s probably safe to dye your hair during pregnancy. However, if you’re concerned, you might consider waiting until the second trimester, when your developing baby is less vulnerable. You might also consider streaking, highlighting, frosting or other options in which the chemicals have little or no contact with your scalp.
Exposure to paint fumes has not been shown to harm developing fetuses. However, you may wish to avoid prolonged exposure if the smell bothers you.
INTRODUCTION — There are four major types of high blood pressure that may occur during pregnancy:
●Preeclampsia superimposed upon chronic hypertension
●Gestational hypertension (also called transient hypertension)
This topic will review high blood pressure related to preeclampsia, the treatment of preeclampsia, and the possible complications of preeclampsia.
WHAT IS PREECLAMPSIA? — Many women with preeclampsia have smaller than normal blood vessels feeding the placenta. Abnormalities in the development of these blood vessels very early in pregnancy appear to initiate a cascade of events that eventually cause high blood pressure (hypertension) and the other signs and symptoms of the disease. However, why this happens to some women and not others is not completely understood.
Most women with preeclampsia gradually develop hypertension and excess protein in the urine (proteinuria). Some women develop hypertension and other signs of the disease without developing proteinuria. Signs of preeclampsia can appear anytime during the last half of pregnancy (after 20 weeks of pregnancy) or in the first few days postpartum, and typically resolve within a few days after delivery.
Preeclampsia is sometimes called by other names, including toxemia, pregnancy-induced hypertension, and preeclamptic toxemia. It is mild in most cases. One severe form of preeclampsia is called HELLP syndrome (H = hemolysis, EL = elevated liver enzymes, LP = low platelets). A woman is said to have eclampsia if she has one or more seizures and has no other conditions that could have caused the seizure.
In the United States, preeclampsia occurs in 3 to 4 percent of pregnancies. Most cases occur at or near term (after 37 weeks of pregnancy), although 10 percent of cases occur before 34 weeks of pregnancy.
Chronic hypertension — Chronic hypertension is defined as a blood pressure ≥140/90 mmHg diagnosed before pregnancy, before the 20th week of pregnancy, or that persists more than 12 weeks after delivery.
Chronic hypertension with superimposed preeclampsia — This term describes a woman with chronic hypertension who develops signs of preeclampsia after the 20th week of pregnancy.
Gestational hypertension — Women with gestational hypertension have all of the following:
●Blood pressure ≥140/90 mmHg
●No protein in the urine (proteinuria)
●Pregnancy duration of at least 20 weeks
●No previous history of high blood pressure.
Over time, some pregnant women with gestational hypertension will develop proteinuria or other signs of preeclampsia and be considered preeclamptic, while others will be diagnosed with chronic hypertension because of persistently high blood pressure after delivery.
WOMEN AT RISK FOR PREECLAMPSIA — There are no tests that can reliably predict who will get preeclampsia, and there is no way to completely prevent it. Women with one or more of the following characteristics have an increased risk of developing preeclampsia:
●First pregnancy (excluding miscarriages)
●High blood pressure, kidney disease, lupus, or diabetes prior to pregnancy
●Multiple gestation (eg, twins or triplets)
●A family history of preeclampsia in a sister or mother
●A previous history of preeclampsia
●Age under 20 years and possibly age over 35 to 40 years
Conversely, women who do not develop preeclampsia in their first pregnancy are at low risk of developing it in a subsequent pregnancy.
Doctors may recommend that women who have risk factors that place them at high risk of developing preeclampsia take low-dose aspirin starting in the late first trimester and continuing into the third trimester of pregnancy to reduce this risk . Examples of high-risk women include women with a history of early onset preeclampsia with delivery before 34 weeks of gestation or preeclampsia in more than one pregnancy. Low-dose aspirin is not recommended for women at low or average risk of developing preeclampsia.
PREECLAMPSIA SIGNS AND SYMPTOMS — Signs and symptoms of preeclampsia occur, in part, due to changes inside the small arteries that decrease blood flow to major maternal organs such as the kidney, brain, and liver, as well as the placenta.
Maternal — Most women with preeclampsia never experience anything more than mild high blood pressure and a small amount of excess protein in the urine. These changes do not cause symptoms; therefore, prenatal visits to check blood pressure and measure urinary protein are scheduled frequently in the last half of pregnancy.
Signs of severe disease — Preeclampsia can worsen and develop features of severe disease. This usually occurs over several days to weeks, but may occur more quickly. Severe features of preeclampsia consist of one or more of the following signs or symptoms. However, the symptoms may be subtle, and patients should not hesitate to mention any concerns about possible symptoms of preeclampsia to their provider:
Symptoms of severe disease:
●Persistent severe headache
●Visual problems (blurred or double vision, blind spots, flashes of light or squiggly lines, loss of vision)
●New shortness of breath (due to fluid in the lungs)
●Pain in the mid- or right-epigastrium (similar to heartburn)
Signs of severe disease:
●Blood pressure ≥160/110 mmHg. Women with blood pressures in this range have an increased risk of stroke.
●Abnormal kidney tests (eg, serum creatinine >1.1 mg/dL)
●Low platelet count
●Liver abnormalities (detected by blood tests)
●Pulmonary edema (fluid in the lungs)
Fetal — Blood flow to the placenta carries oxygen and nutrients from mother to baby. Preeclampsia can reduce blood flow to the placenta, which can the following effects on the baby:
●Abnormal nonstress test or biophysical profile score (see 'Fetal monitoring' below)
●Slowed growth of the baby, based upon an ultrasound
●Decreased amount of amniotic fluid around the baby, noted on ultrasound
●Decreased blood flow through the umbilical cord, noted on Doppler tests (performed during ultrasound).
PREECLAMPSIA MANAGEMENT — The only cure for preeclampsia is delivery of the baby and placenta. Although bedrest and taking high blood pressure medication can lower blood pressure and thus reduce the risk of stroke, these treatments do not improve the abnormalities in the mother's blood vessels and prevent progression of the disease.
At term — Pregnancies complicated by preeclampsia without severe features (formerly mild preeclampsia) are delivered at 37 weeks (ie, term) because delivery is the most effective treatment for preeclampsia. This helps to minimize the risk of harm to the woman or her baby from worsening preeclampsia. Babies at or near term are not at high risk of complications from prematurity and usually will not need to spend time in a special care nursery.
Before term — If preeclampsia occurs before term and there are no severe features of the disease, it may be possible to delay delivery to allow the baby more time to grow and mature, while monitoring the woman and baby closely. If severe features of preeclampsia occur before term, delivery is often necessary to prevent complications in the woman or her baby. In the setting of preeclampsia with severe features, if both the maternal and fetal statuses are reassuring then delivery can be delayed up to but not beyond 34 weeks.
The method of delivery (vaginal or cesarean birth) depends upon a number of factors, such as the position of the baby, the dilation and effacement (thinning) of the cervix, and the baby's condition. In most situations, vaginal delivery is possible.
Steroids — Babies delivered prematurely are at risk for breathing problems because their lungs may not be fully developed. Women who are likely to require preterm delivery (at or before 34 weeks of pregnancy) are usually given two steroid injections (eg, betamethasone) to speed fetal lung development. The steroids also decrease other potential complications of preterm birth, such as intraventricular hemorrhage (bleeding into the brain). The two injections are given 24 hours apart, and the full benefit of the treatment occurs 48 hours after the first injection. A second course of steroids may be needed if more than a few weeks have passed from the initial course and delivery becomes necessary, and provided that an additional delay of delivery for 24 to 72 hours is medically appropriate.
Maternal monitoring — When delivery is delayed, the mother and baby will be monitored. The woman may be admitted to the hospital or may be allowed to stay at home and have frequent office visits. Women who are at home should call their healthcare provider immediately if any symptoms of severe disease develop (see 'Maternal' above).
Maternal monitoring usually includes blood pressure measurements and blood and urine tests to check liver and kidney function, and platelet counts.
Fetal monitoring — Fetal monitoring includes a combination of nonstress tests and ultrasound examination.
Non-stress testing is performed to monitor the baby's condition. It is done by measuring the baby's heart rate with a small device that is placed on the mother's abdomen. The device uses sound waves (ultrasound) to measure the baby's heart rate over time, usually for 15 to 30 minutes. Normally, the baby's baseline heart rate should be between 120 and 160 beats per minute. Normally, an increased rate should occur periodically; the increase should be at least 15 beats per minute above the baseline heart rate for 15 seconds. The test is considered reassuring if two or more fetal heart rate increases are seen within a 20 minute period. Further testing may be needed if these increases are not observed after monitoring for 40 minutes. In general, outpatients undergo fetal testing twice per week, while inpatient testing is often performed daily.
Ultrasound is used to monitor the baby's growth, assess its well-being, and evaluate blood flow through the umbilical cord (called a Doppler test). A biophysical profile assesses well-being by using ultrasound to evaluate the baby's movements, breathing activity, movement of the arms and legs, and amniotic fluid volume.
Induced labor — If the mother or baby's test results are concerning, the healthcare provider will usually recommend delivery. The most common reasons for delivery in women with preeclampsia are listed the table
If the cervix is still closed and long, medications may be applied directly to the cervix to help it open and thin. Most women will also require an intravenous medication, oxytocin (Pitocin), to stimulate the uterus to contract. If labor does not progress with these measures, or if complications develop that require the baby to be delivered quickly, a cesarean birth is usually performed
Preventing seizures — Because women with preeclampsia can develop eclampsia (seizures), most patients are treated with an anticonvulsant medication. Intravenous (IV) magnesium sulfate is the drug most commonly used to prevent seizures. Dietary supplements that contain magnesium are not effective or recommended for prevention of seizures. IV magnesium is safe, although high blood levels of magnesium can be harmful. The mother and baby are monitored closely during treatment. Magnesium is given to the woman during labor and usually for 24 hours after delivery.
Severe hypertension is treated with one or more IV high blood pressure medications to lower the risk of a maternal stroke.
CARE AFTER DELIVERY — High blood pressure and protein in the urine resolve after delivery, usually within a few days. Severe hypertension should be treated, and some women will require a high blood pressure medication after being discharged from the hospital. This can be discontinued when the blood pressure returns to normal levels, usually within six weeks. Your provider may recommend monitoring of blood pressure after discharge from the hospital either at his/her office or at home, and again in about 10 to 14 days to confirm resolution of hypertension. Avoiding nonsteroidal antiinflammatory drugs (NSAIDs) for pain relief may help control persistent hypertension, as these drugs may adversely affect blood pressure and kidney function.
Blood pressure that continues to be elevated beyond 12 weeks after delivery is unlikely to be related to preeclampsia and may require long-term treatment
OUTCOMES — Mildly elevated blood pressure over a few weeks or months is not usually harmful; it does not have the same long-term risks (stroke, heart attack) as chronic high blood pressure. Losing protein in the urine due to preeclampsia does not damage the kidneys. In women with mild features of preeclampsia near term, newborn outcomes are generally good.
Preeclampsia with severe features can cause temporary abnormalities in the woman's liver and kidney function and a low platelet count (thrombocytopenia, which can be associated with bleeding). In women with severe features of the disease, especially those who are preterm, preterm delivery may be required, leading to neonatal problems related to prematurity.
Women who have preeclampsia with severe features that develop before term, recurrent preeclampsia, or gestational hypertension appear to be at increased risk of cardiovascular disease later in life, including during the premenopausal period.
RISK OF PREECLAMPSIA IN FUTURE PREGNANCIES — Most women who experience preeclampsia will not have it in a subsequent pregnancy. The risk of recurrent preeclampsia is between 5 and 70 percent.
●Women who developed severe features of preeclampsia and were delivered before 30 weeks gestation having the highest risk (up to 70 percent) of preeclampsia in future pregnancies.
●Women with preeclampsia without severe features of the disease near term have only a 5 percent chance of developing it again.
●Women with preeclampsia develop high blood pressure (greater than 140/90 mmHg) and generally have protein in their urine, although some women develop other features of the disease without proteinuria. This can occur anytime during the last half of pregnancy (after 20 weeks of gestation) or in the first few days after delivery.
●Preeclampsia occurs in 3 to 4 percent of pregnancies in the United States. It is not known why some women develop preeclampsia while others do not. Currently, there are no tests that can reliably predict who will get the disease, and there is no way to completely prevent it. Taking low-dose aspirin in the late first trimester through the third trimester appears to lower the risk of developing preeclampsia in women at high risk of developing the disease.
●The majority of women with preeclampsia have no symptoms. The disease can worsen and develop severe features characterized by the following signs and symptoms (table 2).
●A pregnant woman should immediately call her healthcare provider if any of the signs or symptoms of severe disease develop, or if she has decreased fetal activity, vaginal bleeding, abdominal pain, or frequent uterine contractions.
●The only cure for preeclampsia is delivery of the baby and placenta. Reduced physical activity, but not strict bed rest, and taking high blood pressure medication can lower the blood pressure but will not stop preeclampsia from worsening or reduce the risk of its complications.
●If tests monitoring the mother’s or baby's condition show concerning results, the healthcare provider may recommend delivery. A vaginal delivery is often possible.
●Because women with preeclampsia can develop seizures (called eclampsia), most women are treated with an anticonvulsant medication. Magnesium sulfate is the drug most commonly used to prevent seizures. It is safe for both mother and baby. It is given intravenously to the mother during labor and usually for 24 hours after delivery.
●High blood pressure and protein in the urine resolve after delivery, usually within a few days. However, some women require medication to reduce high blood pressure after being discharged from the hospital.
●Most women who experience preeclampsia without severe features will not have it in a future pregnancy. The risk of recurrence is higher in women with severe features of preeclampsia, especially when they occur in the second trimester.
●Women who develop preeclampsia appear to be at increased risk of developing cardiovascular disease later in life, so regular health care may be particularly important in this group
Elevated blood pressure after the 20th week of pregnancy. It occurs in 6-7% of all pregnancies, and is most commonly seen with the woman's first pregnancy. If severe and untreated it can cause damage to the kidneys, heart, and brain. The disorder can also lead to pre-eclampsia, a serious complication of pregnancy that may lead to seizures, bleeding, and other problems. Women with gestational hypertension also have a higher incidence of having premature deliveries and low birth weight babies.
Headache, dizziness, visual changes. Often, there are no symptoms.
Common tests used for diagnosis and treatment
A history and physical exam will be performed, including frequent measures of the blood pressure.
Pregnancy (BHCG) test, Complete blood count (CBC), Comprehensive metabolic panel (CMP), Electrocardiogram (EKG), Urinalysis (UA), Ultrasound
Obstetrics and Gynecology
Therapy depends on how high the blood pressure is and the age of the pregnancy. Treatment includes: antihypertensive medications, decreased salt intake, observation and close follow-up, and/or early delivery of the baby.
What is Down syndrome? — Down syndrome is a life-long condition that a person is born with. It can cause learning problems and medical problems affecting the heart, blood, stomach, and other organs (figure 1). The learning and medical problems in people with Down syndrome can be mild or severe.
People with Down syndrome have a problem with their chromosomes. Chromosomes are large structures found in cells that house thousands of genes. People with Down syndrome have an extra chromosome. This causes their problems and makes them look a little different than people without Down syndrome (picture 1).
About 1 in 700 babies is born with Down syndrome. A woman of any age can have a baby with Down syndrome. But a woman is more likely to have a baby with Down syndrome the older she gets. She’s also more likely to have a baby with Down syndrome if she has a close family member with the condition.
What is a screening test for Down syndrome? — A screening test for Down syndrome is a test that can tell you if it is likely that your baby has Down syndrome. Screening tests do not tell you for sure if your baby has Down syndrome. Having a screening test does not increase a woman’s chance of having a miscarriage. A miscarriage is when a pregnancy ends on its own.
If a screening test shows that there is a high chance that a baby has Down syndrome, a woman can have another test to find out for sure.
Which tests can tell for sure if my baby has Down syndrome? — The tests that can do this are called “diagnostic tests.” Two types of diagnostic tests are available:
■Chorionic villus sampling, also called “CVS” – During CVS, a doctor puts a needle into the mother’s uterus and removes a tiny piece of the placenta. The placenta is the organ that brings the baby nutrients and oxygen and carries away waste. CVS is usually done at 11 to 12 weeks of pregnancy, but it can be done as late as 14 weeks.
■Amniocentesis – During amniocentesis, a doctor puts a needle into the mother’s uterus and removes some of the fluid that is around the baby. This test is usually done between 15 and 20 weeks of pregnancy, but it can be done later.
It is important for women to know that diagnostic tests can have side effects. Women who have diagnostic tests have a small chance of having a miscarriage.
Do all women have a screening test for Down syndrome? — No. But all women get to choose if they want to have a screening test. Some women choose to have a screening test, and others choose not to. You can decide if a screening test is right for you.
Are different screening tests available? — Yes. Different screening tests are available depending on:
■How far along a woman is in her pregnancy – Different tests are done at different times during pregnancy.
■Where a woman lives – Different tests are available in different areas.
Screening tests can involve:
■Blood tests – Blood is taken from the mother.
■Ultrasound – This is an imaging test that creates pictures of the baby.
■Both blood tests and ultrasound
Why might a woman choose to have a screening test? — A woman might have a screening test if:
■She wants to know as much as she can about her baby’s health.
■She is worried about her baby. She feels that she will worry less if there is a low chance that her baby has Down syndrome.
■She wants to know if her baby has Down syndrome so that she can:
•Learn about Down syndrome before the baby is born
•Give birth in a hospital that has experience taking care of babies with Down syndrome
•Choose whether to end her pregnancy
Why might a woman choose not to have a screening test? — A woman might skip the test because:
■She feels that “whatever will be, will be,” and knows that she would never end a pregnancy. She will wait until her baby is born to see if it has Down syndrome.
■She knows that she would not have a diagnostic test even if her screening test showed that there was a high chance her baby had Down syndrome.
■She wants to know for sure if her baby has Down syndrome, so she will have a diagnostic test instead of a screening test.
What if my screening test shows that there is a high chance my baby has Down syndrome? — If your screening test shows that there is a high chance your baby has Down syndrome, you can:
■Have a diagnostic test to know for sure if your baby has Down syndrome
■Not have any more tests done during pregnancy. You can wait until birth to have a test done to see if your baby has Down syndrome.
■Talk to an expert called a “genetic counselor” to help you make a choice
How do I know which choice is right for me? — It can be tough to know which choice is right for you. To help you choose, talk with your doctor or nurse about the benefits and downsides of the different tests
INTRODUCTION — Folic acid supplementation and dietary fortification decrease the occurrence and recurrence of neural tube defects (NTDs) and are recommended for women planning pregnancy or capable of becoming pregnant. However, it is estimated that only 15 to 25 percent of folic acid–preventable spina bifida and anencephaly worldwide is being prevented through folic acid supplementation and food fortification programs.
Folic acid supplementation, usually as part of a multivitamin, has also been associated with a variety of benefits unrelated to NTDs.
FOLATE AND FOLIC ACID — Although the terms are used interchangeably, folate is a water-soluble B vitamin (B9) that occurs naturally in foods such as beef liver, leafy green vegetables, oranges, and legumes, whereas folic acid is the synthetic form of folate that is found in supplements and added to fortified foods. The bioavailability of folic acid from supplements and folic acid fortified foods appears to be substantially higher than folate bioavailability from consumption of natural foods. Bioavailability is affected by several factors, including whether the food is raw or cooked, how it is cooked, the combination of foods consumed, and host factors.
Varying degrees of folate deficiency may result from low carbohydrate diets, since bread and pasta are made of fortified grain; some medications (eg, phenytoin, sulfasalazine); high consumption of foods designated as "organic," which are exempt from folic acid fortification regulations; and medical or surgical conditions associated with malabsorption (eg, celiac disease, Crohn's disease, intestinal resection or bypass).
FOLIC ACID SUPPLEMENTATION FOR PREVENTION OF NTDS — Folic acid supplementation can reduce the risk of NTDs, presumably by preventing nutritional deficiency and by overcoming disruptions in folate metabolism related to underlying genetic variation in folate-related genes. Folic acid may enhance cell proliferation for neural closure directly or it may be involved in the epigenetic regulation of expression of genes that control neural closure.
Because neural tube development/closure occurs within the first four weeks of embryonic life (ie, by six weeks of gestation) and before many women know they are pregnant or meet with a clinician, folic acid supplementation should be started at least one month prior to conception and continue throughout the first trimester. The dose (0.4 to 5 mg) depends on the woman's risk status. Furthermore, because many pregnancies are unplanned, folic acid supplementation is recommended for all women of childbearing potential.
High risk women — Women with a previous child with a NTD and those taking anticonvulsants associated with development of NTDs (eg, valproate, carbamazepine) are at highest risk of having an affected child in a future pregnancy. Periconceptional folic acid supplementation (4 to 5 mg) is recommended for these women to reduce the occurrence and recurrence of affected infants. Periconceptional supplementation reduces the risk of recurrent NTDs by about 70 percent.
Women should be advised not to attempt to achieve the 4 mg daily dosage of folic acid by taking multiple multivitamins containing folic acid because of the possibility of ingesting harmful levels of other vitamins, such as Vitamin A. One prenatal vitamin once per day and a 1 mg of folic acid three times per day is a practical means of ingesting a total dose of 4 mg per day.
Previously affected pregnancy — We recommend 4 mg/day folic acid supplementation for patients at high risk of NTDs beginning ≥4 weeks before conception and continuing through the first 12 weeks of pregnancy. The recommendation for folic acid supplementation is based upon results of the United Kingdom's Medical Research Council Vitamin Study Research Group randomized, double-blind prevention trial. The purpose of this trial was to determine whether supplementation with folic acid (4 mg) around the time of conception could prevent NTDs in patients at risk because of a previously affected pregnancy. Pregnancies supplemented with folic acid had a 72 percent reduction in the incidence of NTDs.
Although the 4 mg dose was effective, it is unclear what the minimal effective dose is and whether larger doses would be more effective. Wald has recommended a 5 mg folic acid supplement. The rationale for this approach is that serum folate concentrations increase by 0.94 ng/mL (95% CI 0.77-1.10) for every 0.1 mg/day increase in folic acid intake in women aged 20 to 35 years, and doubling of serum folate concentration roughly halves the risk of a NTD. Therefore, a supplement of 0.4 mg/day should reduce the risk of NTDs by about 36 percent, a supplement of 1 mg/day should reduce the risk of NTDs by about 57 percent, and a supplement of 5 mg/day should reduce the risk of NTDs by about by about 85 percent.
Patient education is critical as many women who have had an NTD-affected pregnancy and are planning a subsequent pregnancy do not take a folic acid supplement.
Anticonvulsant therapy — No trials to determine the effective dose of folic acid supplementation in women taking anticonvulsants have been performed. The 4 mg dose has been suggested based upon extrapolation from studies in women with a previously affected child. In general, preconception doses of folate are continued throughout pregnancy. Some experts suggest that when a woman with epilepsy who is taking anticonvulsants becomes pregnant, plasma folate levels should be monitored and the dose of folic acid adjusted to achieve a concentration above 4 ng/mL (9 nmol/L).
Other conditions — Some experts recommend high dose folic acid supplements for women at intermediate risk of having a child with a NTD (eg, insulin dependent diabetes, obesity with BMI >35 kg/m2, family history of neural tube defect in a second or third degree relative, and women with certain folate-enzyme genotypes, malabsorption disorders, or taking anti-folate medications.
The Society of Obstetricians and Gynaecologists of Canada suggests that women with health risks, including epilepsy, insulin dependent diabetes, BMI >35 kg/m2, family history of NTD, or belonging to a high-risk ethnic or religious group (eg, Sikhs in British Columbia ), increase their dietary intake of folate-rich foods and take daily folate supplementation of 5 mg folic acid, beginning at least three months before conception and continuing until 10 to 12 weeks post conception. They also suggest this approach for women who have a history of poor compliance with medications and lifestyle issues, such as variable diet, inconsistent use of contraception, and use of possible teratogenic substances (alcohol, tobacco, recreational non-prescription drugs), as the higher folic acid dose may provide a more adequate serum red blood cell folate level in the setting of irregular vitamin/folic acid intake.
The effects of folic acid supplementation have not been studied extensively in women at intermediate risk of NTDs. Two case-control studies support the use of folic acid supplementation for reduction of NTDs in women with gestational diabetes and a murine study reported folic acid supplementation of diabetic mice not only reduced the incidence of NTDs (NTD incidence 6 percent versus 28.4 percent in controls), but also cardiovascular and skeletal malformations. In contrast, obesity-mediated NTDs may not be related to folate deficiency and thus may not be reduced by folic acid supplementation, but data are conflicting.
Primary prevention in low risk women — The third National Health and Nutrition Examination Survey (from 1989 to 1991, prior to folate supplementation and food fortification) reported that the mean folate intake of reproductive aged women in the United States was 230 mcg per day. This is below the level that is required to maintain normal blood folate levels during pregnancy, a period of increased folate demand. To prevent folate deficiency and its consequences in periconceptional and pregnant women, folic acid supplementation and food fortification programs were introduced and designed to ensure a minimum daily intake of 400 mcg folate.
Multiple national organizations have conducted educational campaigns to inform women of childbearing age about the need for additional folate intake. Nevertheless, a 2007 Gallup survey found that only 40 percent of women of childbearing age in the United States reported daily consumption of a vitamin containing folic acid, 61 to 89 percent knew that folic acid prevents birth defects, and 6 to 16 percent were aware that it should be taken before conception. Young women (under age 24 years) were the least well-informed.
Folic acid supplements — Most women (95 percent) who deliver infants with NTDs have no history of a prior affected pregnancy and are not on anticonvulsants, therefore, measures to prevent recurrent NTDs will have a small impact on the incidence of this disorder. For this reason, periconceptional folic acid supplementation is recommended for all women of reproductive potential to decrease the occurrence of a first affected pregnancy. This recommendation is supported by a meta-analyses of 41 studies that found use of multivitamin supplements provided consistent protection against NTDs (OR 0.67, 95% CI 0.58-0.77 in case control studies; OR 0.52, 95% CI 0.39-0.69 in cohort and randomized trials).
The minimum dose of folic acid that is effective is unknown; a wide range of doses has been used and found to be effective. The United States Preventive Services Task Force (USPSTF) recommends that all women of reproductive age planning or capable of pregnancy take a supplement containing 0.4 mg to 0.8 mg of folic acid daily to reduce their risk of having a child with a NTD. Maximum benefit is derived from consumption from one month before through two to three months after conception; however, daily intake for all women of childbearing age is advised since over 50 percent of pregnancies in the United States are unplanned. Statements by the American College of Obstetricians and Gynecologists, the American Academy of Family Physicians, and the American Academy of Pediatrics concur with this recommendation.
Doses well above this amount are probably necessary to maximally reduce the risk of neural tube defects; a conservative dose was chosen to minimize the risk of masking B12 deficiency. Another advantage of a dose less than 1 mg is that (in the United States) pills containing 1 or more milligrams of folic acid require a prescription (prescription prenatal vitamins typically contain 1 mg of folic acid). As discussed above, multiple multivitamin pills should not be consumed to achieve this dose because of the risk of vitamin A toxicity.
Consumption of foods fortified with folic acid is also useful (see below). It is reasonable to recommend both a daily multivitamin and consumption of high folate and folic acid fortified foods since folate intake from the latter may be erratic and reduced by dieting, which is common in this age group.
Folate levels can be measured in plasma, serum, and red blood cells. However, plasma and serum levels reflect only the transient concentration of the vitamin between absorption and storage. Red blood cell folate concentration is a more accurate assessment of folate status, although its measurement is not highly reproducible. Due to this variability in measurements and unclear correlation with outcome, we are not recommending routinely measuring folate concentration.
Food fortification — Although folic acid supplements are highly effective in preventing NTDs, supplementation alone is not an effective strategy for prevention because of poor patient compliance. Therefore, in 1998 the US Food and Drug Administration decided to fortify the food supply with folic acid; specifically, the agency mandated that enriched grain products be fortified with 140 micrograms of folic acid per 100 grams of product. This is a low level of fortification; it was designed to ensure that 90 percent of the population consumed <1000 mcg folic acid daily from all sources (food and supplements) and thus not mask vitamin B12 deficiency. The validity of this rationale has been challenged repeatedly.
It is generally believed that food fortification alone is unlikely to provide adequate intake of folic acid for all women, therefore, folic acid supplements are still recommended for women of childbearing age. However, there is also some evidence that current levels of folic acid fortification are sufficient to prevent most folate-sensitive NTDs.
The success of food fortification programs is illustrated by the following representative studies:
●The Centers for Disease Control analyzed data from a population-based surveillance system that included 90 percent of live births in the United States. From 1995-1996 (before mandatory food fortification) to 1998-1999 (after mandatory food fortification), the birth prevalence of all neural tube defects, spina bifida, and anencephaly declined by 19, 23, and 11 percent, respectively. The prevalence of NTDs post-fortification has remained relatively stable since the initial reduction observed immediately after mandatory folic acid fortification. However, the rate of NTDs remains higher among Hispanic women than among non-Hispanic white and black women. This discordancy may be related to differences in eating habits, genetic factors, or the limitations of birth certificate data, which can be inaccurate and do not include stillbirths or pregnancy terminations. Factors other than fortification, such as prenatal serum and ultrasound screening programs for fetal anomalies and women’s attitudes about pregnancy termination, may have contributed to these findings.
●The benefit of national policy of food fortification was also suggested by data from Canada, where the incidence of NTDs (as ascertained in live births, stillbirths, and pregnancy terminations) decreased by about 50 percent after initiation of folic acid fortification of grain products. The greater reduction in NTDs in Canada compared with the United States may be related to more complete ascertainment of cases. A significant reduction in NTDs after food fortification has also been observed in South America.
●In addition, a study including over 60,000 women revealed a 32 percent decrease in the incidence of high MSAFP levels (values greater than 2.75 MoM) since mandatory food fortification was introduced in the United States. Since MSAFP is performed in the midtrimester, this large decrease reflects the combined effects of folic acid supplementation and food fortification on the incidence of NTDs better than data derived from birth certificates. However, since most mothers with elevated MSAFP values do not have fetuses with NTDs and placental factors may cause an elevated MSAFP, folate may be exerting its effects on MSAFP through improved placentation.
Fortified oral contraceptives — A combination tablet containing an oral contraceptive (20 mcg ethinyl estradiol/3 mg drospirenone) and folic acid (451 mcg levomefolate) is available. A decision analysis estimated that if all women in the United States using oral contraceptives used folate-fortified contraceptive pills rather than traditional contraceptive pills, the number of NTDs in these women would fall by 24 to 31 percent. This benefit was based on the assumption that women who had achieved steady-state folate levels would sometimes miss pills, resulting in unplanned pregnancy, and that folate levels would be maintained for 20 weeks after discontinuation of contraception, the period when planned or unplanned pregnancies often occur.
Risks of folic acid supplementation during pregnancy
Infant — No harmful effects from in utero exposure to folic acid have been proven; however, concerns have been raised about potential adverse effects, such as the possibility that maternal folic acid supplementation could influence immune phenotypes via epigenetic mechanisms and increase susceptibility to respiratory diseases in infants. The proposed mechanism is through folic acid’s effect on DNA methylation and subsequent influence on gene expression. Epidemiologic studies have reported inconsistent findings on the association of maternal folic acid exposure or folate levels and increased incidence or severity of childhood respiratory outcomes and atopic disease.
Maternal — A potential harm of folic acid supplementation is the possibility of masking vitamin B12 deficiency, a condition that is rare in reproductive-aged women. Theoretical risks include drug interactions, allergic reactions, carcinogenic effects, and increased twinning. There is no evidence that folic acid supplementation for prevention of NTDs has resulted in masking of vitamin B12 deficiency, allergic reactions, or unexpected drug interactions; an effect on twinning is uncertain. Routine vitamin B12 supplementation is not recommended for women taking folic acid supplements
The long-term risk of folate supplementation during pregnancy was evaluated in a 35-year follow-up of women who participated in a placebo controlled randomized trial of folic acid supplementation in pregnancy performed from 1966 to 1967. A nonsignificant increase in breast cancer mortality occurred in women who received 0.2 or 5 mg folic acid supplementation daily during pregnancy. This result may well have been due to chance. The weight of epidemiologic evidence indicates that low folate levels are associated with an increased risk of breast cancer, thus casting doubt on the findings reported in this study. At this time, no change in the recommendations for folic acid supplementation in pregnancy is appropriate, but further study is clearly warranted.
Treatment failures — Adequate intake of folic acid will not prevent all cases of NTDs. There are situations in which the risk of NTDs may not be reduced by any level of folic acid supplementation (ie, nonfolate sensitive NTDs), such as poor first trimester glycemic control in women with diabetes, hyperthermia, NTDs associated with genetic syndromes, and women with immune factors (presence of antibodies to folate receptors). Although the mechanisms for development of NTDs in these cases are not completely defined, they do not appear to rely primarily upon folate deficiency. The percentage of NTDs that is folic acid preventable is unclear; estimates range from 50 to 70 percent. Because nonfolate sensitive NTDs cannot always be identified with certainty, folic acid supplementation is recommended for all women.
OTHER POSSIBLE BENEFITS OF FOLIC ACID SUPPLEMENTATION IN PREGNANCY — In some meta-analyses, maternal consumption of folic acid-containing prenatal multivitamins was associated with decreased risk for several congenital anomalies, not only NTDs. However, others concluded folic acid, alone or in combination with vitamins and minerals, did not have a clear benefit in reduction of birth defects (other than NTDs), miscarriage, preterm birth, or perinatal death. In individual reports, folic acid supplementation, usually as part of a multivitamin, has been associated with reductions in severe language delay, preeclampsia, preterm birth, growth restriction, some childhood cancers, conotruncal heart defects, and autism spectrum disorders, but these possible benefits require further study and confirmation, as well as assessment of the optimum dose.
Many congenital anomalies may result from complex interactions involving maternal and fetal genomic and epigenetic susceptibilities and environmental factors, such as periconceptional folate deficiency. For example, the MDR1 3435C<T polymorphism appears to modify cellular exposure to potential teratogens, particularly in a low folate environment. In two case-control studies, women who carried this mutation and used a variety of medications without also taking a folic acid supplement during pregnancy appeared to be at higher risk of having a child with cleft lip/palate or congenital heart disease than women who did not have the mutation or who had the mutation and did not use medication.
SUMMARY AND RECOMMENDATIONS
●Folate deficiency can cause neural tube defects and folic acid supplementation can prevent them. Periconceptional folic acid supplementation reduces the incidence of neural tube defects by 50 to 70 percent. (See 'Folic acid supplementation for prevention of NTDs' above.)
●We recommend periconceptional folic acid supplementation to reduce the occurrence and recurrence of neural tube defects (Grade 1A). The optimal dose is unclear. (See 'Folic acid supplementation for prevention of NTDs' above.)
•For women with a previously affected child, we suggest a folic acid supplement of 4 mg per day beginning at least one month prior to conception and continuing through the first trimester (Grade 2B). (See 'High risk women' above.)
•For women taking valproate and carbamazepine, and for women with pregestational diabetes, we suggest 4 mg of folic acid supplementation per day beginning at least one month prior to conception and continuing through the first trimester (Grade 2C). (See 'High risk women' above and "Management of epilepsy and pregnancy".)
•For all other women of reproductive potential, we suggest taking one multivitamin containing 0.4 to 0.8 mg of folic acid daily (Grade 2B). (See 'Folic acid supplements' above.)
●In women with epilepsy, preconception doses of folate are generally continued throughout pregnancy. Some experts suggest monitoring plasma folate levels and adjusting the dose to achieve a concentration above 4 ng/mL (9 nmol/L). (See "Management of epilepsy and pregnancy".)
●Folic acid supplementation will not prevent all neural tube defects, such as those related to chromosomal abnormalities and other nonfolate-related mechanisms. (See 'Treatment failures' above.)