1.      ACOG Technical Bulletin #224—Pulmonary Disease in Pregnancy

2.      ACOG Educational Bulletin #248—Viral Hepatitis in Pregnancy

Thromboembolism

1.      Sacher GN, Sacher RA.  Venous thromboembolism and anticoagulation in pregnancy.

2.      Young GL, Jewell D.  Interventions for varicosities and leg oedema in pregnancy. 

      Cochrane Database Syst Rev 2000;(2):CD001066

3.      Gant NF, Worley RJ, Everett RB, MacDonald PC. Control of vascular responsiveness

      during human pregnancy. Kidney Int 1980 Aug;18(2):253-8

4.      Parker CR Jr, Hauth JC, Goldenberg RL, Cooper RL, Dubard MB.  Umbilical cord

      serum levels of thromboxane B2 in term infants of women who participated in a

      placebo-controlled trial of low-dose aspirin.  J Matern Fetal Med 2000 Jul-Aug;9(4):209-15

5.      Heyborne KD.  Preeclampsia prevention: lessons from the low-dose aspirin therapy trials. 

      Am J Obstet Gynecol 2000 Sep;183(3):523-8

6.      Baldwin GS.  Do NSAIDs contribute to acute fatty liver of pregnancy?  Med Hypotheses

7.      ACOG Practice Bulletin #19—Thromboembolism in Pregnancy

8.      Lindqvist P, Dahlback B, Marsal K.  Thrombotic risk during pregnancy: a population study. 

      Obstet Gynecol 1999;94:730-734

9.      Toglia MR, Weg JG.  Venous thromboembolism during pregnancy. 

      N Engl J Med 1996;335:108-114

10.  ACOG committee opinion #211—Anticoagulation with Low-Molecular-Weight

      Heparin During Pregnancy.

Fever

1.      Andersen AM, Vastrup P, Wohlfahrt J, Andersen PK, Olsen J, Melbye M.

      Fever in pregnancy and risk of fetal death: a cohort study. Lancet 2002

      Nov 16;360(9345):1552-6  (Comment in: Lancet. 2002 Nov 16;360(9345):1526.)

      BACKGROUND: Hyperthermia acts as a teratogen in some animals where it can

      induce resorption of the fetus and fetal death. Fever during pregnancy, especially in

      the period of embryogenesis, is also suspected as being a risk factor for fetal death

      in human beings. We did a large cohort study in Denmark to investigate this possibility.

      METHODS: We interviewed 24040 women who were recruited in the first half of

      pregnancy to the Danish National Birth Cohort Study, and obtained information on

      the number of fever incidents during the first 16 weeks of pregnancy. For each

      fever episode, the highest measured body temperature, duration of incident, and

      gestational age were recorded. Outcomes of pregnancies were identified through

      linkage with the Civil Registration System and the National Discharge Registry.

      Cox's regression with time-dependent variables was used to estimate the relative

      risk of fetal death, taking delayed entry into account. FINDINGS: 1145 pregnancies

      resulted in a miscarriage or stillbirth (4.8%). During the first 16 pregnancy weeks

      18.5% of the women experienced at least one episode of fever. However, we found

      no association between fever in pregnancy and fetal death before or after adjustment

      for known risk factors of fetal death (relative risk 0.95 [95% CI 0.80-1.13]).

      This finding was consistent irrespective of measured maximum temperature,

      duration and number of fever incidents, or the gestational time of the fever incident,

      and was observed for fetal death in all three trimesters of pregnancy.

      INTERPRETATION: We found no evidence that fever in the first 16 weeks of

      pregnancy is associated with the risk of fetal death in clinically recognised pregnancies.

 

2.      Shin JH, Shiota K. Folic acid supplementation of pregnant mice suppresses heat-induced

      neural tube defects in the offspring. J Nutr 1999 Nov;129(11):2070-3  Neural tube

      defects (NTD) are a group of malformations that result from the failure of the neural

      tube to close early in embryonic development and among the most common congenital

      malformations in humans. It has been reported that a substantial proportion of NTD in

      humans can be prevented by folic acid (FA) supplementation prior to conception and

      during the first months of pregnancy, and myo-inositol (MI) was shown to reduce the

      incidence of NTD in curly tail mice which are not prevented by FA. Brief maternal

      hyperthermia (HT) early in pregnancy has been implicated in NTD both in humans

      and laboratory animals, and anterior NTD including exencephaly and anencephaly

      are induced frequently when pregnant mice are exposed to HT. We examined the effect

      of FA or MI supplementation of pregnant mice on the occurrence of heat-induced NTD

      in the offspring. When pregnant mice were treated with FA (3 mg/kg) daily from

      gestational day (GD) 0.5 through GD 9.5 and heated at GD 8.5, the prevalence of NTD

      in the fetuses (26.6%) was significantly lower than the corresponding figure in the HT

      alone group (38.6%; P < 0.05). However we failed to detect the preventive effect of MI

      (500 mg/kg). The results of this study suggest that prenatal FA supplementation

      decreases HT-induced NTD in mice and sufficient FA intake during early pregnancy

      may be recommended to avoid the birth of malformed children.

 

3.      Lynberg MC, Khoury MJ, Lu X, Cocian T. Maternal flu, fever, and the risk of neural tube

      defects: a population-based case-control study. Am J Epidemiol 1994 Aug 1;140(3):244-55 

      Results of clinical and epidemiologic studies have shown an increased risk for neural

      tube defects (NTD) in infants whose mothers were exposed to heat during pregnancy.

      However, the risk for NTD in infants whose mothers had influenza during pregnancy

      has not been well studied. This population-based case-control study of infants born in

      metropolitan Atlanta, Georgia, from 1968 through 1980 included 385 infants with NTD,

      3,647 infants with other birth defects, and 2,676 infants without birth defects. Of the

      385 mothers of case infants, 31 reported having a 2-day or longer episode of flu with

      fever from 1 month before through 3 months after conception (odds ratio

      (OR) = 3.0; 95% confidence interval (CI) 1.9-4.7). Infants of mothers who took

      medications for their episodes of flu with fever had an even higher risk for NTD

      (OR = 4.3, 95% CI 2.6-7.1). When mothers of infants with birth defects other than

       NTD were used as controls, an increased risk of NTD remained for flu with fever

       (OR = 1.7, 95% CI 1.1-2.5). There was no increased risk for NTD among the infants

      of mothers who reported fever from causes other than flu. Because of the heterogeneity

      of maternal flu, the individual contributions of infection, fever, and medications remain

      difficult to disentangle.

4.      Milunsky A, Ulcickas M, Rothman KJ, Willett W, Jick SS, Jick H. Maternal heat exposure

      and neural tube defects. : JAMA 1992 Aug 19;268(7):882-5  OBJECTIVE--To determine

      if exposure to hot tub, sauna, fever, or electric blanket during early pregnancy was

      associated with an increased risk for neural tube defects (NTDs). DESIGN--Prospective

      follow-up study. SETTING--Mostly private obstetric practices, primarily in New England.

      PARTICIPANTS--A cohort of 23,491 women having serum alpha-fetoprotein screening

      or an amniocentesis were identified. Complete exposure and outcome information was

      available for 97% of these women. OUTCOME MEASURES--Relative risks (RRs) were

      used to compare incidence of NTD in those exposed to heat with those who were not

       exposed to any heat. Crude RRs were calculated directly from the data. Unconfounded

      RRs were calculated using logistic regression. RESULTS--Women reporting any heat

       exposure (sauna, hot tub, fever, or electric blanket) in early pregnancy had a crude risk

      of their fetuses developing NTD of 1.6 (95% CI [confidence interval], 0.9 to 2.9).

       Women reporting exposure to sauna, hot tub, or fever in early pregnancy had a crude

       risk of their fetuses developing NTD 2.2 times that of women without heat exposure

      (95% CI, 1.2 to 4.1). For hot tub use, the crude RR was 2.9 (95% CI, 1.4 to 6.3); for

      sauna, 2.6 (95% CI, 0.7 to 10.1); for fever, 1.9 (95% CI, 0.8 to 4.1); and for electric

      blanket, 1.2 (95% CI, 0.5 to 2.6). Multivariate adjusted RRs for individual heat sources,

      after controlling for maternal age, folic acid supplements, family history of NTD, and

      exposure to other heat sources, were for hot tub use, 2.8 (95% CI, 1.2 to 6.5); sauna,

      1.8 (95% CI, 0.4 to 7.9); fever, 1.8 (95% CI, 0.8 to 4.1); and electric blanket, 1.2

      (95% CI, 0.5 to 2.6). When only hot tub, sauna, and fever were considered and the

      women's exposure to each tallied, compared with no heat exposure, the RR for NTDs

      increased from 1.9 (95% CI, 0.9 to 3.7) after one type of heat exposure to 6.2

      (95% CI, 2.2 to 17.2) after two types of heat exposure. CONCLUSIONS--Exposure to

      heat in the form of hot tub, sauna, or fever in the first trimester of pregnancy was

      associated with an increased risk for NTDs. Hot tub exposure appeared to have the

      strongest effect of any single heat exposure. Exposure to electric blanket was not

      materially associated with increased risk for NTDs

 

Asthma1.       Tan KS, Thomson NC  Asthma in pregnancy. Am J Med 2000 Dec 15;109(9):727-33 Although about 1% of pregnant women have asthma, it is often underrecognized and suboptimally treated. The course of asthma during pregnancy varies; it improves, remains stable, or worsens in similar proportions of women. The risk of an asthma exacerbation is high immediately postpartum, but the severity of asthma usually returns to the preconception level after delivery and often follows a similar course during subsequent pregnancies. Changes in beta(2)-adrenoceptor responsiveness and changes in airway inflammation induced by high levels of circulating progesterone have been proposed as possible explanations for the effects of pregnancy on asthma. Good control of asthma is essential for maternal and fetal well-being. Acute asthmatic attacks can result in dangerously low fetal oxygenation. Chronically poor control is associated with pregnancy-induced hypertension, preeclampsia, and uterine hemorrhage, as well as greater rates of cesarian section, preterm delivery, intrauterine growth retardation, low birth weight, and congenital malformation. Women with well-controlled asthma during pregnancy, however, have outcomes as good as those in their nonasthmatic counterparts. Inhaled therapies remain the cornerstone of treatment; most appear to be safe in pregnancy.2.       Kallen B, Rydhstroem H, Aberg A.  Asthma during pregnancy--a population based study. Eur J Epidemiol 2000 Feb;16(2):167-71 To study delivery outcome in women with asthma, using Swedish health registers. Women with asthma were identified in two ways: by information in interviews performed by midwives at the pregnant woman's first visit to antenatal care, and by linkage between a medical birth register and a hospital discharge register, identifying women who had been hospitalized for asthma and also had a delivery. Births between 1984 and 1995 were studied. An increased risk for preterm birth and low birth weight was seen, possibly co-varying with disease severity. Also a significant increase in pregnancies of more than 41 weeks duration was noticed. An increase in infant death but not in congenital malformations rate was observed. An association with preeclampsia, gestational diabetes, and infant hypoglycemia was verified. Maternal asthma appears to be a risk factor for preterm and postterm births and increases the risk for some pregnancy complications.3.      Jadad AR, Sigouin C, Mohide PT, Levine M, Fuentes M Risk of congenital malformations associated with treatment of asthma during early pregnancy. Lancet 2000 Jan 8;355(9198):119 Studies assessing the risk of congenital malformations associated with the treatment of asthma during the first trimester of pregnancy are few, have limited power and support continuation of treatment.4.      Biedermann KJ, Kuhn M. [Lung diseases in pregnancy] [Article in German]. Ther Umsch 1999 Oct;56(10):589-96. Pulmonary diseases play a particular role during pregnancy. First, the adaptive hyperventilation of the mother implies sufficient pulmonary reserves, and second, and increasing oxygen consumption of the fetus during pregnancy might be compromised by maternal hypoxemia and could be followed by fetal growth retardation and fetal hypoxemia. Asthma bronchiale is the leading pulmonary disease in pregnancy and is not associated with higher risk for pregnancy and fetus when sufficiently threatened. First line medicaments are beta-2-agonists and steroids. Pneumonia however is a serious menace to the pregnant women, especially when not early diagnosed and correctly treated. Respecting the leading germs, macrolids or wide-spectrum penicillins are used. Tuberculosis has no deleterious effect on pregnancy with early diagnosis and treatment, which follows the usual guidelines during pregnancy with isoniacid, rifampicin and ethambutol. Cystic Fibrosis is not a strict contraindication for a pregnancy, especially for mild clinical forms. However, preconceptional counseling and regular clinical controls before and during pregnancy are indispensible. Deep vein thrombosis and pulmonary embolism are more frequent during pregnancy; the search for risk factors, prophylaxis and treatment are essential to avoid these complications. Heparin is the ideal prophylaxis and treatment in pregnancy, while oral anticoagulants should be avoided because of their effect on the fetus.5.      Cydulka RK, Emerman CL, Schreiber D, Molander KH, Woodruff PG, Camargo CA Jr. Acute asthma among pregnant women presenting to the emergency department. Am J Respir Crit Care Med 1999 Sep;160(3):887-92. Asthma complicates up to 4% of pregnancies. Our objective was to compare emergency department (ED) visits for acute asthma among pregnant versus nonpregnant women. We performed a prospective cohort study, as part of the Multicenter Asthma Research Collaboration. ED patients who presented with acute asthma underwent a structured interview in the ED, and another by telephone 2 wk later. The study was performed at 36 EDs in 18 states. A total of 51 pregnant women and 500 nonpregnant women, age 18 to 39, were available for analysis. Pregnant women did not differ from nonpregnant women by duration of asthma symptoms (median: 0.75 versus 0.75 d, p = 0.57) or initial peak expiratory flow rate (PEFR) (51% versus 53% of predicted, p = 0.52). Despite this similarity, only 44% of pregnant women were treated with corticosteroids in the ED compared with 66% of nonpregnant women (p = 0.002). Pregnant women were equally likely to be admitted (24% versus 21%, p = 0.61) but less likely to be prescribed corticosteroids if sent home (38% versus 64%, p = 0.002). At 2-wk follow-up, pregnant women were 2.9 times more likely to report an ongoing exacerbation (95% CI, 1.2 to 6.8). Among women presenting to the ED with acute asthma, pregnant asthmatics are less likely to receive appropriate treatment with corticosteroids. Stroke1.      Pfausler B, Vollert H, Bosch S, Schmutzhard E. Cerebral Venous Thrombosis - A New Diagnosis in Travel Medicine? J Travel Med 1996 Sep 1;3(3):165-167. Cerebral venous thrombosis is a syndrome seen in association with a large number of disease processes. The commonest reported causes in adults are oral contraception,1 pregnancy and complications associated with the postpartum period,2 systemic malignancy,3 and infection.4 In approximately 20% of adult cases reported during the past 20 years no etiology was established.5 Cerebral venous thrombosis can be caused by similar mechanisms, such as venous thrombosis, occurring elsewhere in the body, e.g., blood vessel wall alterations attributable to inflammation, infection, or invasion of malignant cells, as well as from changes in blood flow due to dehydration and changes in the coagulability of the blood (e.g., from use of oral contraception). PC Gates and HJM Barnett list 38 causes of cerebral venous thrombosis that were proven by angiography or autopsy. One item on their list was dehydration/ hyperpyrexia.5 Recently thrombosis of the venae saphena or femoralis/iliaca has been reported to occur in long distance air travelers.6 We would like to report on five patients (out of 15) in whom cerebral venous thrombosis was causatively linked with either long distance air travel alone, air travel and diarrhea, or air travel and exposure to tropical heat. Nausea & vomiting 2.      Snell LH, Haughey BP, Buck G, Marecki MA. Metabolic crisis: hyperemesis gravidarum. J Perinat Neonatal Nurs 1998 Sep;12(2):26-37. Nausea and vomiting during pregnancy affect approximately 50% to 70% of all pregnant women. Although most cases of nausea and vomiting in pregnancy resolve spontaneously and are not associated with compromised nutritional status, a small percentage of cases progress to hyperemesis gravidarum (severe nausea and vomiting during pregnancy). Hyperemesis gravidarum is a serious disorder that can lead to weight loss, dehydration, electrolyte disturbances, and occasionally death if improperly treated or left untreated. The article summarizes recent research on hyperemesis gravidarum, focusing on the definition, etiology, epidemiology, and current treatment of symptoms.3.      Nelson-Piercy C. Treatment of nausea and vomiting in pregnancy. When should it be treated and what can be safely taken? Drug Saf 1998 Aug;19(2):155-64. Nausea and vomiting are both common in early pregnancy. Most cases are mild and do not require treatment. However, persistent vomiting and severe nausea can progress to hyperemesis if the woman is unable to maintain adequate hydration, and fluid and electrolyte as well as nutritional status are jeopardised. Hyperemesis gravidarum is a diagnosis of exclusion, characterised by prolonged and severe nausea and vomiting, dehydration, ketosis and bodyweight loss. Investigation may show hyponatraemia, hypokalaemia, a low serum urea level, metabolic hypochloraemic alkalosis and ketonuria. The haematocrit is raised and the specific gravity of the urine is increased. There may be associated liver function test abnormalities and abnormal thyroid function tests, with biochemical thyrotoxicosis with raised free thyroxine levels and/or suppressed thyroid-stimulating hormone levels. The pathophysiology of hyperemesis is poorly understood. Various hormonal, mechanical and psychological factors have been implicated. Studies have demonstrated a direct relationship between the severity of hyperemesis, the degree of biochemical hyperthyroidism and the levels of human chorionic gonadotrophin (hCG). Management of hyperemesis should include hospitalisation, intravenous fluid and electrolyte replacement, thiamine (vitamin B1) supplementation, use of conventional antiemetics and psychological support. Most patients improve spontaneously with the help of the above measures without long term sequelae. Conventionally, antiemetics are not usually prescribed, especially before 12 weeks gestation, except for women with hyperemesis. This reluctance relates to fears which are often unfounded concerning the teratogenic effects of antiemetics. Severe hyperemesis, refractory to conventional management with intravenous fluids and antiemetics is a rare, miserable and disabling condition, associated with multiple hospital admissions, time away from work and the family, and psychological morbidity. If inadequately or inappropriately treated, it may cause Wernicke's encephalopathy, central pontine myelinolysis and death. In extreme cases, women may request, or their obstetricians recommend, termination of the pregnancy. There are uncontrolled data supporting a beneficial effect of corticosteroids in these women, and a randomised placebo-controlled trial is currently in progress.4.      Tsang IS, Katz VL, Wells SD. Maternal and fetal outcomes in hyperemesis gravidarum. Int J Gynaecol Obstet 1996 Dec;55(3):231-5. OBJECTIVE: This study sought to evaluate maternal characteristics and pregnancy outcomes among women with hyperemesis gravidarum. METHODS: We performed a retrospective analysis of pregnancy records of obstetric admissions during a 6-year period. Women treated as out-patients for hyperemesis were also identified. Hyperemesis was defined as excessive nausea and vomiting resulting in dehydration, extensive medical therapy, and/or hospital admission. Statistical analysis was by t-test and chi square. RESULTS: We identified 193 women (1.5%) who developed hyperemesis among 13,053 women. Racial status, marital status, age, and gravidity were similar between the hyperemesis patients and the general population. However, there were less women with hyperemesis who were para 3 or greater. Forty-six women (24%) required hospitalization for hyperemesis, mean hospital stay 1.8 days, range 1-10 days. One patient required parenteral nutrition, two had yeast esophagitis, none had HIV infection, psychiatric pathology or thyroid disease. Pregnancy outcomes between hyperemesis patients and the general population were similar for mean birth weight, mean gestational age, deliveries less than 37 weeks, Apgar scores, perinatal mortality or incidence of fetal anomalies. Our incidence of hyperemesis (1.5%) is similar to that of other published reports. CONCLUSION: Women with hyperemesis have similar demographic characteristics to the general obstetric population, and have similar obstetric outcomes.5.      van Stuijvenberg ME, Schabort I, Labadarios D, Nel JT. The nutritional status and treatment of patients with hyperemesis gravidarum. Am J Obstet Gynecol 1995 May;172(5):1585-91. OBJECTIVE: The objective of this study was to evaluate the nutritional status of patients with hyperemesis gravidarum and the effect of a treatment regimen administered during hospitalization. STUDY DESIGN: This was a descriptive, controlled study of 20 patients with hyperemesis gravidarum whose nutritional status was assessed and compared with that of 20 pregnant, nonvomiting matched controls. Blood nutrient status was reassessed after 10 days of treatment with an intravenous saline solution containing a multivitamin preparation and again at day 20. RESULTS: Mean dietary intake of most nutrients fell below 50% of the recommended dietary allowances and differed significantly (p < 0.01) from that of controls. More than 60% of the patients had suboptimal biochemical status of thiamine, riboflavin, vitamin B6, vitamin A, and retinol-binding protein. Vitamin C, calcium, albumin, hematocrit, and hemoglobin values were significantly higher in those patients where the duration of vomiting had been longer, suggesting the presence of dehydration. Treatment was associated with cessation of vomiting and improvement in blood nutrient status. Pregnancy outcome was favorable in all patients. CONCLUSION: The hyperemetic pregnant patient is at nutritional risk; prompt initiation of corrective therapy is recommended.Headache 1.      Maggioni F, Alessi C, Maggino T, Zanchin G. Headache during pregnancy. Cephalalgia 1997 Nov;17(7):765-9. A questionnaire was submitted to 430 women 3 days after delivery, asking mainly about features of headache before and during pregnancy, and their possible modification or recurrence; moreover, delivery modalities and the condition of the newborn were evaluated. One-hundred-and-twenty-six (29.3%) were found to be primary headache sufferers (IHS criteria, 1988), 81 of whom had migraine without aura (MO), 12 migraine with aura (MA), and 33 tension-type headache (TH). In all three groups, about 80% showed complete remission or a higher than 50% decrease in the number of attacks. The improvement was more evident after the end of the first trimester; this trend was common to the three primary headaches considered. In our series of primary headaches, there was only one case (MO) which began during pregnancy. In a subgroup of pluripara, headache maintained the improvement presented in the first pregnancy also during the following gravidic periods in about 50% of cases, whereas in the remaining 50% a worsening in parallel with successive pregnancies was found. Primary headaches "per se" do not seem to increase the pregnancy or delivery risks, nor the vitality of the newborn. During pregnancy, drug use was very much reduced and was restricted to a limited number of compounds.2.      Paulson GW. Headaches in women, including women who are pregnant. Am J Obstet Gynecol 1995 Dec;173(6):1734-41.  There are new concepts in headache definition and pathophysiologic characteristics, but both classification and management remain largely the responsibility of the principal care physician. Women are particularly vulnerable for some types of headache. When a woman needs medical help she usually turns to their personal physician, who can be expected to diagnose and successfully treat most headaches.3.      Baxi LV, Gindoff PR, Pregenzer GJ, Parras MK.  Fetal heart rate changes following maternal administration of a nasal decongestant. Am J Obstet Gynecol 1985 Dec 1;153(7):799-800. Repeated use of a long-acting sympathomimetic amine in the form of a nasal spray was associated with a nonreactive nonstress test and late decelerations in a patient at 41 weeks of gestation. Six hours after the last dose, these changes gradually disappeared.