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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
The symptoms and discomforts of pregnancy are those presentations and conditions that result from pregnancy but do not significantly interfere with activities of daily living or pose a threat to the health of the mother or baby. This is in contrast to pregnancy complications. Sometimes a symptom that is considered a discomfort can be considered a complication when it is more severe. For example, nausea (morning sickness) can be a discomfort, but if, in combination with significant vomiting it causes a water-electrolyte imbalance, it is a complication known as hyperemesis gravidarum.
Common symptoms and discomforts of pregnancy include:
- Tiredness.
- Constipation
- Pelvic girdle pain
- Back pain
- Braxton Hicks contractions. Occasional, irregular, and often painless contractions that occur several times per day.
- Edema (swelling). Common complaint in advancing pregnancy. Caused by compression of the inferior vena cava and pelvic veins by the uterus leads to increased hydrostatic pressure in lower extremities.
- Increased urinary frequency. A common complaint, caused by increased intravascular volume, elevated glomerular filtration rate, and compression of the bladder by the expanding uterus.
- Urinary tract infection
- Varicose veins. Common complaint caused by relaxation of the venous smooth muscle and increased intravascular pressure.
- Haemorrhoids (piles). Swollen veins at or inside the anal area. Caused by impaired venous return, straining associated with constipation, or increased intra-abdominal pressure in later pregnancy.
- Regurgitation, heartburn, and nausea.
- Stretch marks
- Breast tenderness is common during the first trimester, and is more common in women who are pregnant at a young age.
In addition, pregnancy may result in pregnancy complication such as deep vein thrombosis or worsening of an intercurrent disease in pregnancy.
Signs of a miscarriage include vaginal spotting, abdominal pain or cramping, and fluid or tissue passing from the vagina. Bleeding can be a symptom of miscarriage, but many women also have bleeding in early pregnancy and don't miscarry. Bleeding during pregnancy may be referred to as a threatened miscarriage. Of those who seek clinical treatment for bleeding during pregnancy, about half will miscarry. Miscarriage may be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing.
Hyperemesis gravidarum is the presence of severe and persistent vomiting, causing dehydration and weight loss. It is more severe than the more common morning sickness and is estimated to affect 0.5–2.0% of pregnant women.
Gestational diabetes is when a woman without diabetes develops high blood sugar levels during pregnancy.
Miscarriage, also known as spontaneous abortion and pregnancy loss, is the natural death of an embryo or fetus before it is able to survive independently. Some use the cutoff of 20 weeks of gestation, after which fetal death is known as a stillbirth. The most common symptom of a miscarriage is vaginal bleeding with or without pain. Sadness, anxiety and guilt often occur afterwards. Tissue and clot-like material may leave the uterus and pass through and out of the vagina. When a woman keeps having miscarriages, infertility is present.
Risk factors for miscarriage include an older parent, previous miscarriage, exposure to tobacco smoke, obesity, diabetes, thyroid problems, and drug or alcohol use. About 80% of miscarriages occur in the first 12 weeks of pregnancy (the first trimester). The underlying cause in about half of cases involves chromosomal abnormalities. Diagnosis of a miscarriage may involve checking to see if the cervix is open or closed, testing blood levels of human chorionic gonadotropin (hCG), and an ultrasound. Other conditions that can produce similar symptoms include an ectopic pregnancy and implantation bleeding.
Prevention is occasionally possible with good prenatal care. Avoiding drugs, alcohol, infectious diseases, and radiation may prevent miscarriage. No specific treatment is usually needed during the first 7 to 14 days. Most miscarriages will complete without additional interventions. Occasionally the medication misoprostol or a procedure such as vacuum aspiration is used to remove the remaining tissue. Women who have a blood type of rhesus negative (Rh negative) may require Rho(D) immune globulin. Pain medication may be beneficial. Emotional support may help with negative emotions.
Miscarriage is the most common complication of early pregnancy. Among women who know they are pregnant, the miscarriage rate is roughly 10% to 20%, while rates among all fertilisation is around 30% to 50%. In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40. Risk begins to increase around the age of 30. About 5% of women have two miscarriages in a row. Some recommend not using the term "abortion" in discussions with those experiencing a miscarriage in an effort to decrease distress.
Pregnancy, also known as gestation, is the time during which one or more offspring develops inside a woman. A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy can occur by sexual intercourse or assisted reproductive technology. Childbirth typically occurs around 40 weeks from the last menstrual period (LMP). This is just over nine months, where each month averages 29½ days. When measured from conception it is about 38 weeks. An embryo is the developing offspring during the first eight weeks following conception, after which, the term "fetus" is used until birth. Symptoms of early pregnancy may include missed periods, tender breasts, nausea and vomiting, hunger, and frequent urination. Pregnancy may be confirmed with a pregnancy test.
Pregnancy is typically divided into three trimesters. The first trimester is from week one through 12 and includes conception. Conception is when the sperm fertilizes the egg. The fertilized egg then travels down the fallopian tube and attaches to the inside of the uterus, where it begins to form the embryo and placenta. The first trimester carries the highest risk of miscarriage (natural death of embryo or fetus). The second trimester is from week 13 through 28. Around the middle of the second trimester, movement of the fetus may be felt. At 28 weeks, more than 90% of babies can survive outside of the uterus if provided with high-quality medical care. The third trimester is from 29 weeks through 40 weeks.
Prenatal care improves pregnancy outcomes. Prenatal care may include taking extra folic acid, avoiding drugs and alcohol, regular exercise, blood tests, and regular physical examinations. Complications of pregnancy may include disorders of high blood pressure, gestational diabetes, iron-deficiency anemia, and severe nausea and vomiting among others. Term pregnancy is 37 to 41 weeks, with early term being 37 and 38 weeks, full term 39 and 40 weeks, and late term 41 weeks. After 41 weeks, it is known as post term. Babies born before 37 weeks are preterm and are at higher risk of health problems such as cerebral palsy. Delivery before 39 weeks by labor induction or caesarean section is not recommended unless required for other medical reasons.
About 213 million pregnancies occurred in 2012, of which, 190 million were in the developing world and 23 million were in the developed world. The number of pregnancies in women ages 15 to 44 is 133 per 1,000 women. About 10% to 15% of recognized pregnancies end in miscarriage. In 2013, complications of pregnancy resulted in 293,000 deaths, down from 377,000 deaths in 1990. Common causes include maternal bleeding, complications of abortion, high blood pressure of pregnancy, maternal sepsis, and obstructed labor. Globally, 40% of pregnancies are unplanned. Half of unplanned pregnancies are aborted. Among unintended pregnancies in the United States, 60% of the women used birth control to some extent during the month pregnancy occurred.
The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does "not" include any risks conferred by pharmaceutical agents or their metabolites in breast milk.
Every drug has specific information listed in its product literature. The British National Formulary used to provide a table of drugs to be avoided or used with caution in pregnancy, and did so using a limited number of key phrases, but now Appendix 4 (which was the Pregnancy table) has been removed. Appendix 4 is now titled "Intravenous Additives". However, information that was previously available in the former Appendix 4 (pregnancy) and Appendix 5 (breast feeding) is now available in the individual drug monographs.
Breastfeeding and medications is the description of the medications that can be used by a breastfeeding mother with no or few consequences and those medications which are recommended to be avoided. Some medications are excreted in breastmilk. Almost all medicines pass into breastmilk in small amounts. Some have no effect on the baby and can be used while breastfeeding. The National Institutes of Medicine (US) maintains a database containing information on drugs and other chemicals to which breastfeeding mothers may be exposed. It includes information on the levels of such substances in breast milk and infant blood, and the possible adverse effects in the nursing infant. Suggested therapeutic alternatives to those drugs are provided, where appropriate. All data are derived from reliable sources. Some medications and herbal supplements can be of concern. This can be because the drug can accumulate in breastmilk or have effects on the infant and the mother. Those medications of concern are those medications used to treat substance and alcohol addiction. Other medications of concern are those that are used in smoking cessation. Pain medications and antidepressants need evaluation.
Drug use during pregnancy can have temporary or permanent effects on the fetus. Any drug that acts during embryonic or fetal development to produce a permanent alteration of form or function is known as a teratogen. Drugs may refer to both pharmaceutical drug and recreational drugs.
HIV in pregnancy is the presence of the HIV virus in a woman while pregnant. There are concerns because women diagnosed with HIV/AIDS may transmit the infection to their child during pregnancy. The infection be transmitted to the infant during the pregnancy, childbirth, or breastfeeding. However, the risk of mother-to-child transmission of HIV may be reduced by the use of HIV medications known as antiretroviral therapy (ART). These medications may be used by women before, during, and after pregnancy. After delivery, children are also given the medication to reduce the risk of infection. Because HIV may be spread through breast milk, mothers with the infection are encouraged to avoid breastfeeding.
Infection with HIV/AIDS is not a contraindication to pregnancy. Women with the disease may choose to become pregnant if they desire, however, they are encouraged to talk with their doctors beforehand. Some women are unaware they have the disease until they become pregnant. In this case, they should begin antiretroviral therapy as soon as possible. With the appropriate treatment, the risk of mother-to-child infection can be reduced to below 1%. Without treatment, the risk of transmission is 15-45%.
There are approximately 1.4 million HIV positive women who become pregnant and contribute to more than 300,000 neonatal and fetal deaths each year. With the use of ART, transmission of HIV from the mother to child has decreased according to reports by the World Health Organization (WHO). In 2009, there were an estimated 400,000 children born with HIV and by 2013, there were 240,000. Countries in Southern Africa are worst affected by the HIV/AIDS pandemic. In 2010, 30% of all pregnancies in the region were affected by HIV. In 2011, HIV was responsible for 50% of the deaths for children below the age of 5. In the United States, fewer than 200 babies are born with HIV every year.
As of 2015, Cuba has become the first country in the world to eradicate mother-to-child transmission of HIV. In 2010, the WHO partnered with the Pan American Health Organization (PAHO) to implement an initiative that would provide early prenatal care and HIV testing for all pregnant women in the country. For women who tested positive, ART was provided for both the mother and child, cesarean sections were performed, and alternatives to breastfeeding were provided. In implementing these measures, the country was successfully able to eradicate HIV transmission during pregnancy.
Preterm infants usually show physical signs of prematurity in reverse proportion to the gestational age. As a result, they are at risk for numerous medical problems affecting different organ systems.
- Neurological problems include apnea of prematurity, hypoxic-ischemic encephalopathy (HIE), retinopathy of prematurity (ROP), developmental disability, transient hyperammonemia of the newborn, cerebral palsy and intraventricular hemorrhage, the latter affecting 25 percent of babies born preterm, usually before 32 weeks of pregnancy. Mild brain bleeds usually leave no or few lasting complications, but severe bleeds often result in brain damage or even death. Neurodevelopmental problems have been linked to lack of maternal thyroid hormones, at a time when their own thyroid is unable to meet postnatal needs.
- Cardiovascular complications may arise from the failure of the ductus arteriosus to close after birth: patent ductus arteriosus (PDA).
- Respiratory problems are common, specifically the respiratory distress syndrome (RDS or IRDS) (previously called hyaline membrane disease). Another problem can be chronic lung disease (previously called bronchopulmonary dysplasia or BPD).
- Gastrointestinal and metabolic issues can arise from neonatal hypoglycemia, feeding difficulties, rickets of prematurity, hypocalcemia, inguinal hernia, and necrotizing enterocolitis (NEC).
- Hematologic complications include anemia of prematurity, thrombocytopenia, and hyperbilirubinemia (jaundice) that can lead to kernicterus.
- Infection, including sepsis, pneumonia, and urinary tract infection
A study of 241 children born between 22 and 25 weeks who were currently of school age found that 46 percent had severe or moderate disabilities such as cerebral palsy, vision or hearing loss and learning problems. 34 percent were mildly disabled and 20 percent had no disabilities, while 12 percent had disabling cerebral palsy.
Preterm birth causes a range of problems.
The main categories of causes of preterm birth are preterm labor induction and spontaneous preterm labor. Signs and symptoms of preterm labor include four or more uterine contractions in one hour. In contrast to false labour, true labor is accompanied by cervical dilatation and effacement. Also, vaginal bleeding in the third trimester, heavy pressure in the pelvis, or abdominal or back pain could be indicators that a preterm birth is about to occur. A watery discharge from the vagina may indicate premature rupture of the membranes that surround the baby. While the rupture of the membranes may not be followed by labor, usually delivery is indicated as infection (chorioamnionitis) is a serious threat to both fetus and mother. In some cases, the cervix dilates prematurely without pain or perceived contractions, so that the mother may not have warning signs until very late in the birthing process.
A review into using uterine monitoring at home to detect contractions and possible preterm births in women at higher risk of having a preterm baby found that it did not reduce the number of preterm births. The research included in the review was poor quality but it showed that home monitoring may increase the number of unplanned antenatal visits and may reduce the number of babies admitted to special care when compared with women receiving normal antenatal care.
Abortion is the ending of pregnancy by removing a fetus or embryo before it can survive outside the uterus. An abortion that occurs spontaneously is also known as a miscarriage. An abortion may be caused purposely and is then called an induced abortion, or less frequently, "induced miscarriage". The word "abortion" is often used to mean only induced abortions. A similar procedure after the fetus could potentially survive outside the womb is known as a "late termination of pregnancy".
When allowed by law, abortion in the developed world is one of the safest procedures in medicine. Modern methods use medication or surgery for abortions. The drug mifepristone in combination with prostaglandin appears to be as safe and effective as surgery during the first and second trimester of pregnancy. Birth control, such as the pill or intrauterine devices, can be used immediately following abortion. When performed legally and safely, induced abortions do not increase the risk of long-term mental or physical problems. In contrast, unsafe abortions (those performed by unskilled individuals, with hazardous equipment, or in unsanitary facilities) cause 47,000 deaths and 5 million hospital admissions each year. The World Health Organization recommends safe and legal abortions be available to all women.
Around 56 million abortions are performed each year in the world, with about 45% done unsafely. Abortion rates changed little between 2003 and 2008, before which they decreased for at least two decades as access to family planning and birth control increased. , 40% of the world's women had access to legal abortions without limits as to reason. Countries that permit abortions have different limits on how late in pregnancy abortion is allowed.
Historically, abortions have been done using herbal medicines, sharp tools, with force, or through other traditional methods. Abortion laws and cultural or religious views of abortions are different around the world. In some areas abortion is legal only in specific cases such as rape, problems with the fetus, poverty, risk to a woman's health, or incest. In many places there is much debate over the moral, ethical, and legal issues of abortion. Those who oppose abortion often maintain that an embryo or fetus is a human with a right to life and may compare abortion to murder. Those who favor the legality of abortion often hold that a woman has a right to make decisions about her own body.
Symptoms may include abdominal pain or vaginal bleeding during pregnancy. As this is nonspecific in areas where ultrasound is not available the diagnosis was often only discovered during surgery to investigate the abnormal symptoms. They are typically diagnosed later in the developing world than the developed. In about half of cases from a center in the developing world the diagnosis was initially missed.
It is a dangerous condition as there can be bleeding into the abdomen that results in low blood pressure and can be fatal. Other causes of death in people with an abdominal pregnancy include anemia, pulmonary embolus, coagulopathy, and infection.
The determination of the safety of a medication can be evaluated by considering the following:
- The age and maturity of the infant. Full term infants are better able to metabolize medications than premature infants
- The weight of the infant.
- The amount and percentage of breastmilk consumed by the infant. An infant taking solid foods with breastfeeding will receive a lower dose of medication.
- The general health of the infant and the general health of the mother.
- The nature of the mother's illness, if present.
- The general information about the drug other literature documenting studies related to the drug and breastfeeding.
- The duration of the drug therapy.
- Is the drug short-acting? A short-acting form of the drug may be a better choice for a breastfeeding mother rather than a longer-acting form that stays in the mother's system for a longer period.
- How is the medication being given?
- Does the drug interfere with lactation?
The apprehension is not necessarily data driven and is a cautionary response to the lack of clinical studies in pregnant women. The indication is a trade-off between the adverse effects of the drug, the risks associated with intercurrent diseases and pregnancy complications, and the efficiency of the drug to prevent or ameliorate such risks. In some cases, the use of drugs in pregnancy carries benefits that outweigh the risks. For example, high fever is harmful for the fetus in the early months, thus the use of paracetamol (acetaminophen) is generally associated with lower risk than the fever itself. Similarly, diabetes mellitus during pregnancy may need intensive therapy with insulin to prevent complications to mother and baby. Pain management for the mother is another important area where an evaluation of the benefits and risks is needed. NSAIDs such as Ibuprofen and Naproxen are probably safe for use for a short period of time, 48–72 hours, once the mother has reached the second trimester. If taking aspirin for pain management the mother should never take a dose higher than 100 mg.
Spontaneous abortion, also known as miscarriage, is the unintentional expulsion of an embryo or fetus before the 24th week of gestation. A pregnancy that ends before 37 weeks of gestation resulting in a live-born infant is known as a "premature birth" or a "preterm birth". When a fetus dies in utero after viability, or during delivery, it is usually termed "stillborn". Premature births and stillbirths are generally not considered to be miscarriages although usage of these terms can sometimes overlap.
Only 30% to 50% of conceptions progress past the first trimester. The vast majority of those that do not progress are lost before the woman is aware of the conception, and many pregnancies are lost before medical practitioners can detect an embryo. Between 15% and 30% of known pregnancies end in clinically apparent miscarriage, depending upon the age and health of the pregnant woman. 80% of these spontaneous abortions happen in the first trimester.
The most common cause of spontaneous abortion during the first trimester is chromosomal abnormalities of the embryo or fetus, accounting for at least 50% of sampled early pregnancy losses. Other causes include vascular disease (such as lupus), diabetes, other hormonal problems, infection, and abnormalities of the uterus. Advancing maternal age and a woman's history of previous spontaneous abortions are the two leading factors associated with a greater risk of spontaneous abortion. A spontaneous abortion can also be caused by accidental trauma; intentional trauma or stress to cause miscarriage is considered induced abortion or feticide.
Signs in mares appear ten to fourteen days after breeding to an infected or carrier stallion. A gray to creamy vulvar discharge mats the hair of the buttocks and tail, although in many cases, the discharge is absent and the infection is not apparent. Most mares recover spontaneously, although many become carriers. Infected mares are usually infertile during the acute illness. However, the infertility only lasts a few weeks, after which pregnancy is possible.
Stallions do not show signs of infection. The first indication of the carrier state is lack of pregnancy in the mares covered by the stallion.
Swelling (especially in the hands and face) was originally considered an important sign for a diagnosis of pre-eclampsia. However, because swelling is a common occurrence in pregnancy, its utility as a distinguishing factor in pre-eclampsia is not high. Pitting edema (unusual swelling, particularly of the hands, feet, or face, notable by leaving an indentation when pressed on) can be significant, and should be reported to a health care provider.
In general, none of the signs of pre-eclampsia are specific, and even convulsions in pregnancy are more likely to have causes other than eclampsia in modern practice. Further, a symptom such as epigastric pain may be misinterpreted as heartburn. Diagnosis, therefore, depends on finding a coincidence of several pre-eclamptic features, the final proof being their regression after delivery.
An abdominal pregnancy can be regarded as a form of an ectopic pregnancy where the embryo or fetus is growing and developing outside the womb in the abdomen, but not in the Fallopian tube, ovary or broad ligament.
While rare, abdominal pregnancies have a higher chance of maternal mortality, perinatal mortality and morbidity compared to normal and ectopic pregnancies; on occasion, however, a healthy viable infant can be delivered.
Because tubal, ovarian and broad ligament pregnancies are as difficult to diagnose and treat as abdominal pregnancies, their exclusion from the most common definition of abdominal pregnancy has been debated.
Others—in the minority—are of the view that abdominal pregnancy should be defined by a placenta implanted into the peritoneum.
Rh disease (also known as rhesus isoimmunisation, Rh (D) disease, rhesus incompatibility, rhesus disease, RhD hemolytic disease of the newborn, rhesus D hemolytic disease of the newborn or RhD HDN) is a type of hemolytic disease of the newborn (HDN). The disease ranges from mild to severe, and typically occurs only in some second or subsequent pregnancies of Rh negative women where the fetus's father is Rh positive, leading to a Rh+ pregnancy. During birth, the mother may be exposed to the infant's blood, and this causes the development of antibodies, which may affect the health of subsequent Rh+ pregnancies. In mild cases, the fetus may have mild anaemia with reticulocytosis. In moderate or severe cases the fetus may have a more marked anaemia and erythroblastosis fetalis (hemolytic disease of the newborn). When the disease is very severe it may cause hydrops fetalis or stillbirth.
Rh disease is generally preventable by treating the mother during pregnancy or soon after delivery with an intramuscular injection of anti-RhD immunoglobulin (Rho(D) immune globulin). The RhD protein is coded by the RHD gene.
Prenatal cocaine exposure (PCE), theorized in the 1970s, occurs when a pregnant woman uses cocaine and thereby exposes her fetus to the drug. "Crack baby" was a term coined to describe children who were exposed to crack (freebase cocaine in smokable form) as fetuses; the concept of the crack baby emerged in the US during the 1980s and 1990s in the midst of a crack epidemic. Other terms are "cocaine baby" and "crack kid". Early studies reported that people who had been exposed to crack in utero would be severely emotionally, mentally, and physically disabled; this belief became common in the scientific and lay communities. Fears were widespread that a generation of crack babies were going to put severe strain on society and social services as they grew up. Later studies failed to substantiate the findings of earlier ones that PCE has severe disabling consequences; these earlier studies had been methodologically flawed (e.g. with small sample sizes and confounding factors). Scientists have come to understand that the findings of the early studies were vastly overstated and that most people who were exposed to cocaine "in utero" do not have disabilities.
No specific disorders or conditions have been found to result for people whose mothers used cocaine while pregnant. Studies focusing on children of six years and younger have not shown any direct, long-term effects of PCE on language, growth, or development as measured by test scores. PCE also appears to have little effect on infant growth.
However, PCE is associated with premature birth, birth defects, attention deficit hyperactivity disorder, and other conditions. The effects of cocaine on a fetus are thought to be similar to those of tobacco and less severe than those of alcohol. No scientific evidence has shown a difference in harm to a fetus between crack and powder cocaine.
PCE is very difficult to study because it very rarely occurs in isolation: usually it coexists with a variety of other factors, which may confound a study's results. Thus, studies have failed to clearly show that PCE has negative cognitive effects, partly because such effects may be due to concurrent factors. Pregnant mothers who use cocaine often use other drugs in addition, or they may be malnourished and lacking in medical care. Children in households where cocaine is abused are at risk of violence and neglect, and those in foster care may experience problems due to unstable family situations. Factors such as poverty that are frequently associated with PCE have a much stronger influence on children's intellectual and academic abilities than does exposure to cocaine in isolation. Thus researchers have had difficulty in determining which effects result from PCE and which result from other factors in the children's histories.
HELLP syndrome is defined as hemolysis (microangiopathic), elevated liver enzymes (liver dysfunction), and low platelets (thrombocytopenia). This condition may occur in 10–20% of patients with severe pre-eclampsia and eclampsia and is associated with increased maternal and fetal morbidity and mortality. In 50% of instances, HELLP syndrome develops preterm, while 20% of cases develop in late gestation and 30% during the post-partum period.
Cocaine use during pregnancy can be discovered by asking the mother, but sometimes women will not admit to having used drugs. Mothers may lie for fear of prosecution or having their children taken away, but even when they are willing to tell the truth their memories may not be very accurate. It may also not be possible to be sure of the purity of the drug they have taken. More reliable methods for detecting cocaine exposure involve testing the newborn's hair or meconium (the infant's earliest stool). Hair analysis, however, can give false positives for cocaine exposure, and a newborn may not have enough hair to test. The newborn's urine can be tested for cocaine and metabolites, but it must be collected as soon as possible after birth. It is not known how long after exposure the markers will still show up in a newborn's urine. The mother's urine can also be tested for drugs, but it cannot detect drugs used too far in the past or determine how much or how often the drugs were used. Tests cannot generally detect cocaine use over a week prior to sample collection. Mothers are more honest about cocaine use when their urine is also tested, but many users still deny it. Both maternal and neonatal urine tests can give false negatives.
About 66% of women have both nausea and vomiting while 33% have just nausea.