Excessive Prenatal Supplementation of Iodine and Fetal Goiter: Report of Two Cases Using Three-dimensional Ultrasound and Magnetic Resonance Imaging.

Fetal thyroid complications in pregnancy are uncommon, and are commonly related to the passage of substances through the placenta. The excessive iodine intake during the pregnancy is a well-known mechanism of fetal thyroid enlargement or goiter, and invasive procedures have been proposed for the treatment of fetal thyroid pathologies. In the present report, we demonstrate two cases from different centers of prenatal diagnosis of fetal thyroid enlargement and/or goiter in three fetuses (one pair of twins, wherein both fetuses were affected, and one singleton pregnancy). The anamnesis revealed the ingestion of iodine by the patients, prescribed from inadequate vitamin supplementation. In both cases, the cessation of iodine supplement intake resulted in a marked reduction of the volume of the fetal thyroid glands, demonstrating that conservative treatment may be an option in those cases. Also, clinicians must be aware that patients may be exposed to harmful dosages or substances during pregnancy.

As complicações fetais da tireoide na gravidez são incomuns e são comumente relacionadas à passagem de substâncias pela placenta. A ingestão excessiva de iodo durante a gravidez é um mecanismo bem conhecido de aumento da tireoide ou bócio fetal, e procedimentos invasivos foram propostos para o tratamento de patologias da tireoide fetal. No presente relato de caso, demonstramos dois casos de diferentes centros de diagnóstico pré-natal de aumento da tireoide fetal e/ou bócio em três fetos (um par de gêmeos, em que ambos os fetos foram afetados, e uma gravidez única). A anamnese revelou a ingestão de iodo pelos pacientes prescrita por suplementação inadequada de vitaminas. Nos dois casos, a interrupção da ingestão de suplemento de iodo resultou em uma redução acentuada do volume das glândulas tireoides fetais, demonstrando que o tratamento conservador pode ser uma opção nestes casos. Além disso, os médicos devem estar cientes de que as pacientes podem ser expostas a doses ou substâncias nocivas durante a gravidez.

Excessive prenatal supplementation of iodine and fetal goiter: report of two cases using three-dimensional ultrasound and magnetic resonance imaging / Suplementação pré-natal excessiva de iodo e bócio fetal: Relato de dois casos utilizando ultrassonografia tridimensional e ressonância magnética

Abstract Fetal thyroid complications in pregnancy are uncommon, and are commonly related to the passage of substances through the placenta. The excessive iodine intake during the pregnancy is a well-known mechanism of fetal thyroid enlargement or goiter, and invasive procedures have been proposed for the treatment of fetal thyroid pathologies. In the present report, we demonstrate two cases from different centers of prenatal diagnosis of fetal thyroid enlargement and/or goiter in three fetuses (one pair of twins, wherein both fetuses were affected, and one singleton pregnancy). The anamnesis revealed the ingestion of iodine by the patients, prescribed from inadequate vitamin supplementation. In both cases, the cessation of iodine supplement intake resulted in a marked reduction of the volume of the fetal thyroid glands, demonstrating that conservative treatmentmay be an option in those cases. Also, clinicians must be aware that patients may be exposed to harmful dosages or substances during pregnancy.

Resumo As complicações fetais da tireoide na gravidez são incomuns e são comumente relacionadas à passagem de substâncias pela placenta. A ingestão excessiva de iodo durante a gravidez é um mecanismo bem conhecido de aumento da tireoide ou bócio fetal, e procedimentos invasivos foram propostos para o tratamento de patologias da tireoide fetal. No presente relato de caso, demonstramos dois casos de diferentes centros de diagnóstico pré-natal de aumento da tireoide fetal e/ou bócio em três fetos (um par de gêmeos, em que ambos os fetos foram afetados, e uma gravidez única). A anamnese revelou a ingestão de iodo pelos pacientes prescrita por suplementação inadequada de vitaminas. Nos dois casos, a interrupção da ingestão de suplemento de iodo resultou em uma redução acentuada do volume das glândulas tireoides fetais, demonstrando que o tratamento conservador pode ser uma opção nestes casos. Além disso, os médicos devem estar cientes de que as pacientes podem ser expostas a doses ou substâncias nocivas durante a gravidez.

Fetal and Neonatal Circulatory Disorders in Twin to Twin Transfusion Syndrome (The Secondary Publication).

Twin to twin transfusion syndrome (TTTS) is a major complication of monochorionic diamniotic (MD) twins, and its onset is known to be associated with placental vascular anastomoses and blood flow imbalance. In a typical case of TTTS, the recipient develops polyhydramnios, weight gain, cardiomegaly and hydrops fetalis in the uterus. In contrast, the donor develops oligohydramnios and intrauterine growth restriction. Recently, the significance of the renin-angiotensin-aldosterone system (RAAS) that transfers from the donor to the recipient has attracted interest in the fetal circulation of TTTS. The donor has decreased renal blood flow due to decreased circulating blood volume. For this reason, the secretion of RAAS hormones is augmented in the fetal kidneys of the donor. In TTTS, these RAAS hormones from the donor transfer to the recipient through the anastomosed vessels. In addition to excess preload, the recipient heart is exposed to excess afterload due to systemic vasoconstriction through RAAS hormones. Commonly occurring complications in the recipient include myocardial hypertrophy, atrioventricular valve regurgitation, and pulmonary valve stenosis or pulmonary atresia. Fetoscopic laser photocoagulation (FLP) has been introduced recently because neither mortality nor neurological morbidity have been satisfactorily improved with conventional treatment. FLP is a curative method that may improve the prognosis of TTTS. In Japan, this procedure has been performed frequently, and positive neurological outcomes have been achieved.

A newborn with seizures born to a mother diagnosed with primary carnitine deficiency.

BACKGROUND: Maternofetal carnitine transport through the placenta is the main route of fetal carnitine uptake. Decreased free carnitine levels discovered by newborn screening has identified many asymptomatic adult women with systemic primary carnitine deficiency (PCD). Here, we presented amplitude integrated electroencephalogram (aEEG) and magnetic resonance imaging (MRI) findings from a neonate with epilepsy whose mother was carnitine deficient. CASE PRESENTATION: A one-day-old female newborn was admitted after experiencing seizures for half a day; status epilepticus was found on the continuous normal voltage background pattern with immature sleep-wake cycling during aEEG monitoring. On T1-weighted, T2-weighted, FLAIR, and DWI head MRI, there were various degrees of hyperintense signals and diffusion restrictions in the deep white matter of the right hemisphere. Tandem mass spectrometry discovered carnitine deficiency on the second day, which elevated to normal by the 9th day before L-carnitine supplementation was started. The patient was treated with phenobarbital after admission. No further seizures were noted by day 5. It was confirmed that the patient's mother had a low level of serum-free carnitine. Gene analyses revealed that the newborn had heterozygote mutations on c.1400C > G of the SLC22A5 gene, and her mother had homozygous mutations on c.1400C > G. The patient had a good outcome at the 8-month follow up. CONCLUSIONS: Maternal carnitine deficiency that occurs during the perinatal period may manifest as secondary epilepsy with cerebral injury in neonates. The short-term neurodevelopmental outcomes were good. Early diagnosis of asymptomatic PCD in female patients can provide guidance for future pregnancies.

Fetal intracranial hemorrhage due to maternal subclinical vitamin K deficiency associated with long-term eating disorder.

Vitamin K deficiency in pregnant women causes intracranial hemorrhage (ICH) in fetuses. Fetal ICH frequently causes life-threatening and persistent neurological damage. However, indicators for preventing fetal ICH are not established. Two pregnant women developed long-term eating disorders caused by psychosis. They were administered intravenous fluid and vitamin supplementation, excluding vitamin K. The intracranial low-hypoechoic area on fetal ultrasound was suggestive of fetal ICH due to vitamin K deficiency. Their neonates showed severe developmental delay. Laboratory analysis revealed a normal prothrombin time, but elevated protein induced by vitamin K absence II. Pregnant women who have eating disorders more than 3 weeks could develop fetal ICH due to maternal subclinical vitamin K deficiency. Illness duration and protein induced by vitamin K absence II of pregnant woman may be indicators for vitamin K administration to prevent fetal intracranial hemorrhage.

[THE FETAL MIDDLE CEREBRAL ARTERY PEAK SYSTOLIC VELOCITY AS A PEDICTOR OF FETAL ANEMIA IN RH-ALLOIMMUNIZED PREGNANCY].

UNLABELLED: Rh-isoimmunization is a pathological condition in which the fetal red blood cells of a Rh (+) fetus are destroyed by the isoantibodies of a Rh (-) woman sensitized in a previous event. Despite of the wide spread implementation of anti D-gammaglobolin prophylaxis this is still the most common cause for fetal anemia. Recently, sonographic measurement of the fetal middle cerebral artery peak systolic velocity (MCA-PSV) has been shown to be an accurate non-invasive test to predict low fetal hemoglobin levels. We present a case report of Rh-alloimmunized pregnancy with moderate fetal anemia, followed-up by weekly MCA-PSV measurements. CASE REPORT: A 37-year-old Rh (-) negative gravida 3, para 1, without anti-D gammaglobolin prophylaxis in her previous pregnancies, presented at 27+0 weeks of gestation (w.g.) for a routine third trimester scan. Subsequent ultrasound measurements of MCA-PSV confirmed a progressive increase of the peak systolic velocities from 40 to 80 cm/sec, as well as a gradual rise in the anti-D titers. The evidence of developing fetal anemia necessitated elective Caesarean section performed at 35 wg. The neonate was admitted in the intensive care unit and required resuscitation, one exchange blood transfusion and several courses of phototherapy. The patient was discharged two weeks post partum. CONCLUSIONS: There is a strong correlation between the high peak systolic velocities in the middle cerebral artery (MCA-PSV) and the low levels of fetal hemoglobin. The high sensitivity and positive predictive value concerning the development of fetal anemia, as well as its good repeatability, makes this non-invasive test a valuable asset in the management of all pregnancies complicated by severe Rh-alloimmunization.

Complications of vitamin D deficiency from the foetus to the infant: One cause, one prevention, but who's responsibility?

Calcium and phosphorus represent building material for bones. The supplier of these bone minerals is the hormone calcitriol, which originates from vitamin D, itself made by sunshine in human skin. Requirement for bone minerals is highest during phases of rapid growth, and no one grows faster than the foetus and the infant, making them particularly vulnerable. Deprivation of calcium, whether through low calcium intake or low vitamin D, leads to serious health consequences throughout life, such as hypocalcaemic seizures, dilated cardiomyopathy, skeletal myopathy, congenital and infantile rickets, and osteomalacia. These 5 conditions are often summarised as 'symptomatic vitamin D deficiency', are fully reversible but also fully preventable. However, the increasing prevalence of rickets and osteomalacia, and the deaths from hypocalcaemic cardiomyopathy, demand action from global health care providers. Clarification of medical and parental responsibilities is a prerequisite to deliver successful prevention programmes. The foetus and infant have the human right to be protected against harm, and vitamin D supplementation has the same public health priority as vaccinations.

Effects of maternal dietary olive oil on pathways involved in diabetic embryopathy.

Maternal diabetes induces a pro-oxidant/pro-inflammatory intrauterine environment related to the induction of congenital anomalies. Peroxisome proliferator activated receptors (PPARs) are transcription factors that regulate antioxidant and anti-inflammatory pathways. We investigated whether maternal diets supplemented with olive oil, enriched in oleic acid, a PPAR agonist, can regulate the expression of PPAR system genes, levels of lipoperoxidation and activity of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in embryos and decidua from diabetic rats. The embryos and decidua from diabetic rats showed reduced expression of PPARs and increased concentration of lipoperoxidation, MMPs and TIMPs, whereas the maternal treatments enriched in olive oil increased PPARδ in embryos and PPARγ and PPARγ-coactivator-1α expression in decidua, and increased TIMPs concentrations and decreased lipoperoxidation and MMPs activity in both tissues. Thus, maternal diets enriched in olive oil can regulate embryonic and decidual PPAR system genes expression and reduce the pro-oxidant/pro-inflammatory environment during rat early organogenesis.

Iodine supplementation during pregnancy and lactation. Position statement of the working group on disorders related to iodine deficiency and thyroid dysfunction of the Spanish Society of Endocrinology and Nutrition.

Severe and mild iodine deficiency during pregnancy and lactation affects thyroid function of the mother and neonate as well as the infant's neuropsychological development. Studies performed in Spain confirm that most women are iodine deficient during pregnancy and lactation. Pregnant and breast feeding women and women planning to become pregnant should take iodine supplements.

Screening for thyroid disease in pregnancy: a review.

Screening for thyroid disease in pregnancy remains a contentious issue. This review presents these diverging views and discusses their reasons as well as the relevant facts. The final aim is to establish the information gaps and limitations - technological or otherwise - which still need to be eliminated in order to settle the debate conclusively. The prevalence of the more common thyroid dysfunctions that occur in and after pregnancy is discussed. The subsequent impact of these disorders on mother and offspring is also described. Special focus is placed on the benefits and setbacks of currently available and newly proposed investigations, which assay serum hormone levels, serum autoantibody levels, and/or use clinical data. It is pointed out that the relevance of screening varies from one region of the world to the other, based on the content of iodine and selenium in food and water. The review then discusses the current major arguments for and against screening, as well as recommendations and proposed alternatives.

Thyroid (dys-)function in normal and disturbed pregnancy.

INTRODUCTION: During pregnancy, physiologic changes in maternal thyroid function take place especially due to hormonal as well as metabolic processes. Human chorionic gonadotropin activates the maternal thyroid gland leading to increased thyroid hormone production. A sufficient availability of maternal thyroid hormones is essential for fetal development, especially during the first trimester of pregnancy, when the fetal thyroid gland is not yet functional. MATERIALS AND METHODS: Current knowledge of thyroid dysfunction including thyroid autoimmunity, hypothyroidism or hyperthyroidism is summarized with special focus on miscarriage and pregnancy disorders. Therefore, a Medline research as well as an analysis of current guidelines on thyroid function and pregnancy was performed. RESULTS: A study focusing on TSH levels in normal and disturbed pregnancies, the risk of miscarriage in association with thyroid autoantibodies, and (subclinical) hypothyroidism in infertile and fertile women were included. CONCLUSION: Maternal thyroid dysfunction negatively affects pregnancy outcome. Besides a routine iodine supplementation in pregnant women and treatment of hypo as well as hyperthyroidism, TSH levels should routinely be measured in women during childbearing years and adjusted to concentrations <2.5 mIU/l in order to optimize maternal health and fetal development.

[Review by expert group in the diagnosis and treatment of anemia in pregnant women. Federación Mexicana de Colegios de Obstetricia y Ginecología]. / Opinión de un grupo de expertos en diagnóstico y tratamiento de la anemia en la mujer embarazada.

BACKGROUND: According to data from the World Health Organization and UNICEF from year 2009, iron deficiency is the most widespread nutritional deficiency worldwide. This deficiency causes an imbalance between needs and iron supply, which consequently results in anemia. Around the world, two million people suffer from anemia, half of which is due to iron deficiency. The most impacted groups are children and teenagers, due to their highest requirements derived from the growing process, and women in their reproductive age, due to their loss of iron derived from menstruating or to their highest iron needs during pregnancy. This increase in needs is not satisfied by the regular diet, since it includes an insufficient amount and/or low bioavailability of iron. PURPOSE: To share with the medical community treating pregnant women the experience of an expert group so that they always bear in mind the repercussions caused by anemia during pregnancy, know more about the diagnostic possibilities and have a reference point for prescribing iron supplements. METHOD: The consensus method was used through the expert panel group technique. Two rounds were taken for structuring the clinical questions. The first one was to facilitate working groups their focusing in the clinical topics and the population of interest; the second one was to aid in posing specific questions observing the Patient, Intervention, Compare and Outcome (PICO) structure. The primary and clinical secondary study variables were defined by the working groups from the previously developed questions and during the face-to-face working period, according to the natural history of the disease: risk factors, diagnostic classification, (either pharmacological or non pharmacological) treatment and prognosis. The level of evidence and clinical recommendation was classified based on the Evidence Classification Level and Clinical Recommendation of the Medicine Group based on Evidence from Oxford University. RESULTS: In Mexico, 20.6% of pregnant women suffer from anemia, especially those between 15 and 16 years old, who prevail in 42.4% and 34.3% percent, respectively. Almost half the cases are due to iron deficiency. This type of anemia is associated with a higher risk of pre-term delivery, of low birth weight and perinatal death. The first assessment of an anemic pregnant woman shall include the medical history, a physical examination and the quantification of the erythrocyte indices, serum concentrations of iron and ferritin. The measurement of this last one has the highest sensitivity and specificity for diagnosing iron deficiency. Daily oral iron supplementation, at a 60-to-120 mg dosage, may correct most of mild-to-moderate anemias. The most appropriate treatment is with iron salts (iron sulfate, polimaltose iron complex or iron fumarate). In case of intolerance to iron sulfate or fumarate, polimaltose iron is a better tolerated option. Treatment shall be administered until the hemoglobin values are > 10.5 g and ferritin is between 300 and 360 microg/dL, and such levels shall be observed for at least one year. Parenteral administration is an alternative for patients with a severe intolerance to oral administration; even when the possibility of anaphylaxis shall be considered it is lower when using ferrous sacarate. Transfusion is reserved for patients with hemoglobin lower than 7 g/dL or having an imminent cardio-respiratory decompensation. CONCLUSIONS: Iron deficiency is the highest prevailing nutritional deficiency worldwide and its consequences during pregnancy may be highly risky for both the mother and her child. Anemia diagnosis may easily be achieved through a blood analysis including the serum ferritin determination. Serum iron measurement shall not be used as the only marker to set the diagnosis. It is important to rule out other causes, in addition to the deficiencies, which produce anemia in a patient. It is essential to suggest the administration of iron supplements not only during the antenatal period but also after birth o even after a miscarriage to fulfill the need for depleted iron. In severe anemias (hemoglobin being lower than 9.0 g/L), iron doses higher than 120 mg a day may be required. Treatment shall always begin orally, and if this is not well tolerated, parenteral administration shall be used.

A review of pathophysiology and management of fetuses and neonates with meconium ileus for the pediatric surgeon.

PURPOSE: Meconium ileus (MI) is the earliest clinical manifestation of cystic fibrosis (CF), occurring in up to 20% of patients with CF. Our aim was to review and integrate current knowledge about the diagnosis and management of fetuses and neonates with MI that may aid the pediatric surgeon in caring for these patients. METHODS: We identified areas of interest including pathophysiology, prenatal diagnosis, nonoperative and operative management, postoperative management, and prognosis. We performed a Medline search using the search term meconium ileus for English language articles published in the last 20 years. We reviewed reference lists to identify other articles of historical significance. RESULTS: Meconium ileus is primarily associated with CF transmembrane (conductance) regulator mutations F508del, G542X, W1282X, R553X, and G551D, and modifier genes have been found to explain approximately 17% of the phenotypic variability. Mouse, pig, and ferret models for CF demonstrate neonatal bowel obstruction mimicking MI. Sonographic findings of hyperechoic masses and dilated bowel in a high-risk fetus are suggestive of MI. Less than 7% of low-risk fetuses with hyperechoic bowel will have MI. Contemporary series of noninvasive management with Gastrografin enema report success rates of 36% to 39%, significantly lower than historical values. The optimal surgical technique remains controversial, although primary anastomosis results in surgical complication rates between 21% and 31%, higher than those noted with delayed anastomosis. Pulmonary function for patients with CF and MI at 15 and 25 years old is similar to those without MI, although height and weight percentiles may be lower. CONCLUSIONS: This review for pediatric surgeons presents an examination of the literature and synthesizes current information about the pathophysiology, prenatal diagnosis, nonoperative and operative management, postoperative management, and prognosis of the patient with CF and MI.

Malformation spectrum induced by ketoconazole after single administration to pregnant rats during the critical period - comparison with vitamin A-induced malformation spectrum.

Azole derivatives have teratogenic effects in rodents. In the present study, malformations and their sensitive windows induced by high-dose ketoconazole (KCZ), an azole derivative, without maternal toxicity were investigated. In addition, the malformation spectrum determined was compared with that induced by vitamin A palmitate (VAP). Pregnant rats were administered a single dose of KCZ by oral gavage on specific individual days from gestational days 8 to 15 (GDs 8-15). Maternal animals were subjected to necropsy on GD 20, and the obtained fetuses were examined for external, visceral and skeletal malformations. The malformation spectrum of VAP was identified from available published data (Noda, Sato, and Udaka, 1982) and a complementary study (single administration of VAP at 1 200 000 IU kg(-1) ). Embryonic lethality was observed in dams given KCZ on GDs 9-12 with peak incidence on GDs 10 and 11 with complete resorption. KCZ induced major malformations included cleft palate, digital anomalies, misshapen limbs and unique discontinuous ribs, and the sensitive window for each was identified. Compared with the malformations induced by VAP, unique malformations (e.g. discontinuous ribs by KCZ, neural tube defects by VAP), similar malformations with similar sensitive windows (e.g. digital and limb malformations) and similar malformations with different sensitive windows (e.g. embryonic lethality and cleft palate) were distinguished, suggesting that the mechanisms of several of the types of KCZ-induced malformation are related to excessive vitamin A.

Middle cerebral artery-peak systolic velocity in dizygotic twins with anti-E alloimmunization.

Middle cerebral artery-peak systolic velocity (MCA-PSV) has been reported to predict fetal anemia with similar accuracy as amniotic ΔOD450 assay. Alloimmunized dizygotic twin pregnancy allows us to compare anemic and non-anemic twins in the same intrauterine environment. We herein present a case of Rh (E)-incompatible dizygotic twin pregnancy, where MCA-PSV could precisely detect the anemia in one of the twins. A 36-year-old woman, whose previous child required exchange transfusion due to hemolytic anemia of newborn (HFDN), conceived twins after in vitro fertilization-embryo transfer. At 24 weeks' gestation, MCA-PSV of twin A and twin B were 23.9 cm/s (0.8 multiples of median; MoM) and 30.7 cm/s (1.0 MoM), respectively. At 31 weeks' gestation, MCA-PSV values of both twins were sharply elevated to nearly 1.4 MoM. Thereafter, MCA-PSV of twin A fell to 1.0 MoM, whereas MCA-PSV of twin B exceeded 1.5 MoM at 34 weeks' gestation. Development of fetal anemia was suspected and emergency cesarean section was performed. Twin B showed moderate anemia with positive direct Coombs' test and was diagnosed as HFDN due to anti-E alloimmunization. Twin B required phototherapy and red cell transfusion, but exchange transfusion was safely obviated.

[Clinical guideline for the diagnosis and treatment of subclinical thyroid dysfunction in pregnancy. Working Group on Subclinical Thyroid Dysfunction of the Spanish Endocrinology Society]. / Guía clínica para el diagnóstico y el tratamiento de la disfunción tiroidea subclínica en la gestación. Grupo de Trabajo sobre la Disfunción Tiroidea Subclínica de la Sociedad Española de Endocrinología.

Subclinical thyroid disease is a biochemical diagnosis and is common during pregnancy. Because of the physiological hormonal changes that take place during pregnancy and the absence of normal ranges for thyroid hormones during this period, subclinical thyroid disease is difficult to interpret during pregnancy. Subclinical hyperthyroidism during pregnancy has few clinical consequences and no treatment is required. In contrast, subclinical hypothyroidism seems to improve with thyroxine treatment. Iodine supplements during pregnancy and lactation, even in iodine-sufficient areas, are also indicated.

[Thyroid disorders during pregnancy]. / Schilddrüsenerkrankungen in der Schwangerschaft.

Thyroid disorders may not only be the cause infertility but also increases the incidence of miscarriages and the morbidity of the pregnancies. During pregnancy the demand of thyroid hormones increases to about 30 - 50 % and the thyroid has to cope with this increase. In Germany the iodine intake has improved significantly during the last 20 years, but still is borderline low with an mean intake of about 120 microg iodide per day. Therefore it is still recommended that pregnant women are supplemented with about 100 - 150 microg of iodide during pregnancy and the time of breast-feeding, to avoid hypothyroidism of the foetus with concomitant delay of the brain development. Not only women with subclinical hypothyroidism, but only elevated TPO antibodies have a significant increase in early miscarriage and preterm delivery. An early supplementation with Levothyroxin despite euthyroidism might reduce these risks. Those women also more frequently develop postpartum thyroiditis. This risk can be reduced by a supplementation with selenium during and after pregnancy. Graves' disease is a rare disorder and only about 0,1 - 0,4 pregnancies are affected. The course of the disease is biphasic, with an exacerbation within the first trimester and an improvement thereafter, but a recurrence after delivery. Overt thyrotoxicosis has to be treated with propylthiouracil, to maintain euthyroidism during pregnancy. The TSH receptor antibodies are transferred to the foetus with the risk of thyrotoxicosis. Special care of the foetus is therefore necessary. Transient mild hyperthyroidism may occur in women with very high HCG levels during the first three months of pregnancy. This often is associated with hyperemesis gravidarum. Subclinical hypothyroidism of the mother will disturb the normal development of the foetus and therefore has to be treated even when TSH is within the upper normal level. Special care is necessary in women with elevated TPO antibodies, because these more often develop postpartum thyroiditis.

Possible roles of zinc nutriture in the fetal origins of disease.

Risk of diseases of metabolism such as atherosclerosis and adult onset diabetes mellitus is increased by fetal malnutrition. Deficiencies of micronutrients essential for methylation are believed to contribute to the phenomenon in part through epigenetic abnormalities. Zinc is one of the nutrients essential for the epigenome. Because the worldwide prevalence of zinc deficiency is at least 20%, fetal zinc deficiency is common. We suggest fetal zinc deficiency contributes to the pathogenesis of metabolic diseases in adults. In support of our thesis, research in experimental models and humans established the essentiality of zinc at all stages of intrauterine and infant life. Experiments in rodents and/or non-human primates found that fetal and/or suckling zinc deficiency impairs neuropsychological functions of progeny and that the effects persist in spite of nutritional rehabilitation. In addition, maternal zinc deficiency in mice is reported to impair immunity of progeny; effects persist in spite of nutritional rehabilitation into the next generation. We suspect that zinc deficiency is a far greater human health problem than is generally recognized.

Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics.

Prevention of congenital cardiovascular defects has been hampered by a lack of information about modifiable risk factors for abnormalities in cardiac development. Over the past decade, there have been major breakthroughs in the understanding of inherited causes of congenital heart disease, including the identification of specific genetic abnormalities for some types of malformations. Although relatively less information has been available on noninherited modifiable factors that may have an adverse effect on the fetal heart, there is a growing body of epidemiological literature on this topic. This statement summarizes the currently available literature on potential fetal exposures that might alter risk for cardiovascular defects. Information is summarized for periconceptional multivitamin or folic acid intake, which may reduce the risk of cardiac disease in the fetus, and for additional types of potential exposures that may increase the risk, including maternal illnesses, maternal therapeutic and nontherapeutic drug exposures, environmental exposures, and paternal exposures. Information is highlighted regarding definitive risk factors such as maternal rubella; phenylketonuria; pregestational diabetes; exposure to thalidomide, vitamin A cogeners, or retinoids; and indomethacin tocolysis. Caveats regarding interpretation of possible exposure-outcome relationships from case-control studies are given because this type of study has provided most of the available information. Guidelines for prospective parents that could reduce the likelihood that their child will have a major cardiac malformation are given. Issues related to pregnancy monitoring are discussed. Knowledge gaps and future sources of new information on risk factors are described.