Trimester Group Research Articles

Low-Molecular-Weight Heparin for Thrombophilia in Pregnant Women

Abstract Objective: Low-molecular-weight heparin (LMWH) is the anticoagulant of choice during pregnancy because it is associated with a low incidence of osteoporosis and thrombocytopenia. Antithrombotic therapy has recently been used to prevent pregnancy loss in high-risk patients with evidence of acquired or congenital thrombophilia. The aim of the present study was to gain further information on the teratogenic potential of LMWH in this patient group. Methods: The study population included 46 patients with a history of recurrent abortions, intrauterine fetal death or intrauterine growth restriction (IUGR) and severe early-onset preeclampsia. Patients with a history of thromboembolism or positive findings for thrombophilia were prescribed LMWH (enoxaparin sodium, 40 mg daily) in combination with low-dose aspirin (100 mg daily) in the first trimester (group 1, n=14) or the second trimester (group 2, n=17); the remaining 15 patients received low-dose aspirin alone (group 3). Results: No significant differences were noted between the groups in the incidence of congenital malformations or abortions, IUGR or preterm deliveries. One infant in group 1 had familial bilateral postaxial polydactyly of the hands and one in group 3 had patent ductus arteriosus. Conclusion: Despite the small size of the study groups, our results support the assumption that the use of LMWH is safe, at least as a teratogenic agent, in patients with thrombophilia throughout pregnancy.

Serum zinc and copper concentrations in Nigerian women with normal pregnancy

The impact of normal pregnancy on serum zinc and copper concentrations and on copper/zinc ratio has been determined in a cross-sectional study of eighty-four healthy pregnant Nigerian women. Fifty-seven healthy non-pregnant women served as controls. Serum zinc and copper levels were determined by atomic absorption spectroscopy. Mean serum copper concentration is significantly higher (P < 0.001) in the pregnant group than in controls [19.74(4.65) and 11.87(2.61) micromol/L respectively], while mean zinc level is significantly lower (P< 0.001) than in controls [4.40(1.34) and 5.54(1.04) micromol/L respectively. Copper/Zinc ratio is also significantly higher than (P<0.001) in the test subject [4.87(1.77) and 2.23(0.75) micromol/L respectively]. One-way analysis of variance shows that the mean serum zinc and copper concentrations and copper/zinc ratio differ significantly (P < 0.01, P < 0.05, and P < 0.05 respectively) between any two of the trimester groups. Furthermore, there is a significant positive correlation between gestational age and copper/zinc ratio (r- 0.201; P < 0.05), and a significant negative correlation between gestational age and serum zinc concentration (r = -0.274; P < 0.01). In normal pregnancy, a negative and positive linear relationship exists between gestational age and serum zinc level and copper/zinc ratio respectively. Serum copper does not show any significant trend throughout gestation, though pregnant subjects have higher mean serum copper level than controls.

Measurement of gallbladder volume with ultrasonography in pregnant women.

Fasting and postprandial gallbladder volumes were investigated using ultrasonography in three groups (10 subjects in each) of healthy women: third trimester pregnant women, postpartum women up to 10 days after giving birth and nonpregnant controls. The scans were performed at 09:00 after a 12 h fast. After the basal measurement was taken, gallbladder volumes were rescanned in 15 min intervals for 60 mins. At the end of this period, all volunteers received a standard liquid test meal, and scans were performed again for 1 h. The mean basal gallbladder volume was 22.2+/-4.2 mL in the nonpregnant (control) group. In the third trimester group, the basal volume was 37.8+/-10.5 mL -70.5% higher than in the nonpregnant group (P<0.001). In the postpartum group, the mean basal volume was 37.9% lower (27.4+/-6.5 mL) than that of the third trimester group (P<0.02). This basal volume was 23.6% greater than that of the control group (P<0.05). After administration of a test meal, the postprandial gallbladder volumes decreased during the first few minutes compared with baseline values. The volumes decreased by 10.2% to 39.8% (23.5+/-7.3 to 34.0+/-10.2; P<0.01) in the third trimester group, by 14.9% to 43.2% (16.6+/-4.3 to 23.3+/-5.5; P<0.01, 0.001) in the postpartum group and by 19.2% to 51.6% (11.9+/-3.5 to 17.9+/-3.6; P<0.02, 0.05, 0.01, 0.001) in the control group. Postprandial mean gallbladder volumes of the third trimester (P<0. 02) and postpartum groups (P<0.02 to 0.01) were significantly different from those of the control group. In conclusion, incomplete emptying of the gallbladder after eating during the third trimester of pregnancy may contribute to cholesterol-gallstone formation, and pregnancy may thus increase the risk of gallstones.

Characterization of human placental explants: morphological, biochemical and physiological studies using first and third trimester placenta.

The primary objective of this study was to characterize an in-vitro model of the human placenta using morphological, biochemical and physiological parameters. Placental villi were obtained from normal first trimester and term pregnancies. The villi were incubated with Dulbecco's modified Eagle's medium: Ham's F12 nutrient mixture in a shaking water bath at 37 degrees C for up to 310 min. The viability was determined by the production of beta human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH) and the incorporation of [3H]thymidine, [3H]L-leucine and L-[U14C]arginine, while ultrastructure was assessed by transmission electron microscopy. In the first and third trimester group, the release into the medium of the intracellular enzyme LDH remained unaltered throughout the experiment. By contrast, beta-HCG concentrations increased linearly and concentrations were higher in the first trimester than term villi (354.5 +/- 37.8 versus 107 +/- 8.1 IU/g villi protein; P < 0.001). Electron microscopy confirmed preservation of tissue viability for up to 4 h of incubation. The incorporation of thymidine (12.2 +/- 2.9 versus 5.2 +/- 0.5 nmol/g villi protein; P < 0.05), leucine (9.4 +/- 2.1 versus 1.9 +/- 0.4 nmol/g villi protein; P < 0.02) and arginine (17 +/- 4.4 versus 4.2 +/- 0.5 nmol/g villi protein; P < 0.05) were markedly higher in early than in term placenta. Furthermore, placental uptake of L-leucine by the first (9.4 +/- 2.1 versus 17 + 4.4 mol/g villi protein; P < 0.001) and third trimester placental villi (1.9 +/- 0.4 versus 4.2 + 0.5 mol/g villi protein; P < 0.001) was less than that of L-arginine. This study describes a simple technique using placental explants to determine relative rates of uptake of substrate amino acids throughout gestation.

Insulin secretion, clearance and sensitivity in Black pregnant and non-pregnant women in Harare, Zimbabwe

To assess whether reported gestational differences in glucose tolerance in Caucasian and Black women could be due to alterations in insulin secretion, clearance or sensitivity. Cross sectional survey. Antenatal Clinic, Harare; Department of Medical Laboratory Sciences, University of Zimbabwe. 90 healthy women in all the trimesters of pregnancy and 30 healthy non-pregnant women of reproductive age. Fasting (basal) plasma insulin, C-peptide and glucose concentration. Fasting plasma C-peptide, C-peptide to insulin ratio and glucose to insulin ratio were used as indices of insulin secretion, hepatic insulin clearance and insulin sensitivity respectively. Not all means of the fasting plasma glucose levels amongst the four groups of women were equal (p < 0.001), with all possible comparisons being significant except for the first and second trimester groups. Among the comparisons of the means of the glucose:insulin ratio in the four groups of women, only the means of the first and second trimester women differed (mean difference = 0.23, honestly significance difference = 0.20). All groups were comparable in the means of plasma insulin, C-peptide levels and the C-peptide:insulin ratio. Since fasting plasma insulin, C-peptide and C-peptide:insulin ratio were not significantly altered in all trimesters of pregnancy, these data suggest normal basal insulin secretion and clearance during gestation in these sub-Saharan African women.

Renal reabsorption of inorganic phosphorus in pregnancy in relation to the calciotropic hormones

To measure renal reabsorption of inorganic phosphorus and the calciotropic hormones in early and late pregnancy. Prospective, cross-sectional study. Endocrine Institute at Assaf Harofeh and E. Wolfson Medical Centers; the Department of Obstetrics and Gynaecology, Sheba Medical Centre and Tel Aviv University. Three groups of healthy women were studied: pregnant women at the end of the first trimester (n = 20), pregnant women at the end of the third, trimester (n = 22), and nonpregnant controls (n = 27). The renal tubular maximal phosphorus reabsorption per decilitre of glomerular filtrate (TmP/GFR) was measured in all women. Circulating levels of intact parathyroid hormone, calcitriol (1,25-dihydroxy vitamin D3) and insulin-like growth factor I were assayed in part of the women (8-11 of each group). TmP/GFR was elevated in the first trimester group (mean 0.263 mmol/L) compared with controls (95% CI 0.07-0.46, P = 0.003). Third trimester values did not differ from controls. Serum calcitriol in the first trimester group was higher (mean difference 17.68 pg/mL) compared with controls (95% CI 3.89-31.47, P = 0.006) and was higher still (mean difference 20.75 pg/mL) in the third trimester group (95% CI 1.01-40.49, P = 0.042). Serum parathyroid hormone in the first trimester group was lower than in controls or the third trimester group: mean differences were 4.40 pg/mL (95% CI-1.40 to 10.15, P = 0.078) and 8.18 pg/mL (95% CI 0.51-15.85, P = 0.019) respectively. Parathyroid hormone levels correlated negatively to calcitriol levels in the combined control and first trimester groups (r = -0.54, P = 0.022) and negatively to TmP/GFR values in the combined three groups (r = -0.68, P = 0.042). First trimester levels of insulin-like growth factor I were lower than those in controls or in the third trimester: mean differences were 10.24 nmol/L (95% CI 2.05-18.43, P = 0.007) and 13.57 nmol/L (95% CI 4.23-22.91, P = 0.003), respectively. The dominant change in mineral metabolism in pregnancy is a rise in calcitriol which most probably is responsible for the relative suppression of parathyroid hormone and thereby for the rise in TmP/GFR in early pregnancy. All the above support the transfer of minerals to the fetus without compromising maternal bone. The significance of circulating insulin-like growth factor I remains unclear.

Second and early third trimester pregnancy termination by extra-amniotic balloon and intracervical PGE 2

Objective: The aim of the study was to investigate the efficacy and safety of an alternative modality using extra-amniotic balloon and intracervical prostaglandin (PG) E 2 for termination of second and early third trimester pregnancies. Method: Thirty-three pregnant women scheduled for legal termination of pregnancy at 15–32 weeks' gestation were included in the study. Each case received extra-amniotic balloon containing 500–800 ml normal saline and two PGE 2 tablets inserted into the cervical canal. Results: All 33 patients achieved a successful termination. The mean induction-to-abortion interval was 12.85 h. There was no significant difference in induction-to-abortion interval between second trimester group and third trimester group. However, the mean duration of balloon distention was longer in the second trimester group. There were no severe complications. Conclusion: The combined use of extra-amniotic balloon and intracervical PGE 2 tablets is effective, safe and convenient for termination of second and early third trimester pregnancy.

Acid-Base State of Cerebrospinal Fluid During Pregnancy and Its Effect on Spread of Spinal Anaesthesia

To assess the possible relationship between changes in acid-base state of cerebrospinal fluid (CSF) and enhanced spread of spinal anaesthesia during pregnancy, we have measured CSF pH, carbon dioxide tension (PCO2) and HCO3- values in 73 women undergoing spinal anaesthesia with hyperbaric amethocaine 8 mg. Patients were allocated to one of four groups according to gestational period: non-pregnant group (n = 13), first trimester group (8-13 weeks, n = 19), second trimester group (14-26 weeks, n = 11) and third trimester group (27-39 weeks, n = 30). The pH of the CSF was greater in the second and third trimester groups than in the non-pregnant group. CSF PCO2 decreased by 0.53-0.8 kPa throughout pregnancy. CSF HCO3- was decreased throughout pregnancy. Overall, no clinically significant correlation was found between maximum cephalad spread of analgesia and CSF pH, PCO2 or HCO3-. We conclude that pregnancy-induced changes in acid-base state of CSF have little effect on the spread of spinal anaesthesia, although there is a clinically different spread of spinal anaesthesia between non-pregnant and pregnant states.

Anticoagulant Therapy in Pregnancy

Background To investigate the adverse effects of anticoagulant therapy during pregnancy in a tertiary care center.Material and methods A prospective study was carried out between 1 January 1977 and 31 December 1994 and included 54 pregnancies in 50 women treated with anticoagulants. In Group I (n=43) oral anticoagulants were replaced for heparin from the sixth until the end of the twelfth week of gestation. In Group II (n= 11) the pregnancy was diagnosed after the ninth week of gestation and acenocoumarol was not substituted. All patients received vitamine K antagonists during the second and third trimesters. Heparin was given after 36 weeks of pregnancy until the tenth day in the postpartum period. Statistical comparisons used Chi square test (with the Yates correction when appropriate) and Student t test. Results. Mechanical heart valve prosthesis was the most frequent indication (68%). There was one artificial heart valve thrombosis during first trimester in Group I and none in Group II (p=0.45). One s...

Anticoagulant Therapy in Pregnancy

Background To investigate the adverse effects of anticoagulant therapy during pregnancy in a tertiary care center. Material and methods A prospective study was carried out between 1 January 1977 and 31 December 1994 and included 54 pregnancies in 50 women treated with anticoagulants. In Group I (n=43) oral anticoagulants were replaced for heparin from the sixth until the end of the twelfth week of gestation. In Group II (n= 11) the pregnancy was diagnosed after the ninth week of gestation and acenocoumarol was not substituted. All patients received vitamine K antagonists during the second and third trimesters. Heparin was given after 36 weeks of pregnancy until the tenth day in the postpartum period. Statistical comparisons used Chi square test (with the Yates correction when appropriate) and Student t test. Results. Mechanical heart valve prosthesis was the most frequent indication (68%). There was one artificial heart valve thrombosis during first trimester in Group I and none in Group II (p=0.45). One spontaneous abortion occurred in each group (p=0.86). Seven cardiac complications (13.7%) occurred during the second and third trimesters. We recorded no thrombotic episode of an artificial heart valve after the first trimester of pregnancy. Hemorrhagic complications occurred in mid pregnancy (one case=2%) and during peripartum (eight cases=16%). Two maternal deaths occurred in the postpartum period, both were linked with the anticoagulant therapy. There was one coumarin embryopathy (Group II: 9%), but no neonatal mortality. Conclusions (1) Hemorrhagic complications occur among 16% of patients receiving anticoagulant therapy during pregnancy. (2) Delivery and postpartum are the most critical periods.

Acid-base state of cerebrospinal fluid during pregnancy and its effect on spread of spinal anaesthesia

To assess the possible relationship between changes in acid-base state of cerebrospinal fluid (CSF) and enhanced spread of spinal anaesthesia during pregnancy, we have measured CSF pH, carbon dioxide tension (PCO2) and HCO3- values in 73 women undergoing spinal anaesthesia with hyperbaric amethocaine 8 mg. Patients were allocated to one of four groups according to gestational period: non-pregnant group (n = 13), first trimester group (8-13 weeks, n = 19), second trimester group (14-26 weeks, n = 11) and third trimester group (27-39 weeks, n = 30). The pH of the CSF was greater in the second and third trimester groups than in the non-pregnant group. CSF PCO2 decreased by 0.53-0.8 kPa throughout pregnancy. CSF HCO3- was decreased throughout pregnancy. Overall, no clinically significant correlation was found between maximum cephalad spread of analgesia and CSF pH, PCO2 or HCO3-. We conclude that pregnancy-induced changes in acid-base state of CSF have little effect on the spread of spinal anaesthesia, although there is a clinically different spread of spinal anaesthesia between non-pregnant and pregnant states.

Anticoagulant therapy in pregnancy

To investigate the adverse effects of anticoagulant therapy during pregnancy in a tertiary care center. A prospective study was carried out between 1 January 1977 and 31 December 1994 and included 54 pregnancies in 50 women treated with anticoagulants. In Group I (n=43) oral anticoagulants were replaced for heparin from the sixth until the end of the twelfth week of gestation and acenocoumarol was not substituted. All patients received vitamin K antagonists during the second and third trimesters. Heparin was given after 36 weeks of pregnancy until the tenth day in the postpartum period. Statistical comparisons used Chi square test (with the Yates correction when appropriate) and Student t test. Mechanical heart valve prosthesis was the most frequent indication (68%). There was one artificial heart valve thrombosis during first trimester in Group I and none in Group II (p=0.45). One spontaneous abortion occurred in each group (p=0.86). Seven cardiac complications (13.7%) occurred during the second and third trimesters. We recorded no thrombotic episode of an artificial heart valve after the first trimester of pregnancy. Hemorrhagic complications occurred in mid-pregnancy (one case=2%) and during peripartum (eight cases=16%). Two maternal deaths occurred in the postpartum period, both were linked with the anticoagulant therapy. There was one coumarin embryopathy (Group II: 9%),but no neonatal mortality. (1) Hemorrhagic complications occur among 16% of patients receiving anticoagulant therapy during pregnancy. (2) Delivery and postpartum are the most critical periods.

Cerebrospinal fluid progesterone in pregnant women

To assess the possible relationship between an increase in progesterone concentration in cerebrospinal fluid (CSF) and enhancement of spread of spinal anaesthesia, we have measured CSF progesterone concentrations in 134 patients undergoing spinal anaesthesia with hyperbaric amethocaine 8 mg. Patients were allocated to one of five groups according to the gestational period: non-pregnant group (n = 13), first trimester group (8-12 weeks, n = 16), second trimester group (13-24 weeks, n = 18), third trimester group (25-36 weeks, n = 38) and term group (37-41 weeks, n = 49). Progesterone concentration in CSF was higher in the third trimester and term groups than in the non-pregnant, first trimester and second trimester groups. Maximum cephalad spread of analgesia was higher in the second trimester, third trimester and term groups than in the non-pregnant and first trimester groups. Although an increase in CSF progesterone concentration in the second trimester group was similar in magnitude to that observed in the first trimester group, enhanced spread of spinal anaesthesia, comparable in magnitude with that observed in the term group, occurred in the second trimester group. There was no significant correlation between CSF progesterone concentration and spread of spinal anaesthesia in any of the groups. These data suggest that not only a minimum level of progesterone in CSF but also a certain duration of exposure to elevated CSF progesterone concentrations may be necessary for enhancement of spread of spinal anaesthesia, and that values of CSF progesterone concentration do not correlate directly with enhancement of spread of spinal anaesthesia.

PREGNANCIES COMPLICATED BY ACUTE APPENDICITIS

Appendicitis is one of the most common acute abdominal conditions that requires operation during pregnancy. The maternal and fetal complications occurring in such situations are well known. However, the diagnostic and therapeutic challenges of acute appendicitis complicating pregnancy persist in current surgical practice. Thirty-eight obstetric cases who had an appendicetomy performed during pregnancy between 1986 and 1993, were reviewed. In 31 cases, acute appendicitis was proven at laparatomy, and by subsequent histopathology. In the confirmed cases, seven occurred in the first trimester, 12 in the second trimester, eight in the third trimester and four in the immediate postpartum period. Two miscarriages occurred in the first trimester group, and two late abortions and two preterm (26 and 28 weeks) deliveries occurred in the second trimester group. In the third trimester/postpartum group, all babies survived, but four patients had Caesarean sections with the appendicetomy and the incidence of perforated/gangrenous appendices was highest. Perinatal outcome was worst, with the highest fetal wastage rate if the acute appendicitis occurred in the second trimester, although maternal morbidity appeared to be the same across different gestational periods.

Spread of subarachnoid hyperbaric amethocaine in pregnant women

In order to examine how the gestational period influences the spread of spinal anaesthesia, we have measured the extent of spinal block produced by hyperbaric amethocaine 8 mg in 90 women. The patients were allocated to one of five groups according to the gestational period: non-pregnant group (n = 17), first trimester group (6-12 weeks, n = 14), second trimester group (13-24 weeks, n = 26), third trimester group (25-36 weeks, n = 15) and term group (37-41 weeks, n = 18). Maximum cephalad spread of analgesia was significantly higher in the second trimester (median T3 (range T9-C6)), third trimester (T3 (T4-C7)) and term groups (T2.5 (T4-C8)) than in the nonpregnant (T4 (T8-T2)) and first trimester groups (T4 (T11-C7)). We found that not only term pregnancy but also second and third trimester pregnancies enhanced the spread of spinal anaesthesia, and that first trimester pregnancy did not affect the spread of spinal anaesthesia.

Altered number of platelet angiotensin II receptors in relation to plasma agonist concentrations in normal and hypertensive pregnancy

The relation between plasma angiotensin II concentrations and the platelet angiotensin II receptor was examined in four different groups of subjects. Platelet receptors were used as representative of physiologically significant sites such as in vascular smooth muscle. A control group consisting of non-pregnant females was studied together with three pregnant groups: normal pregnant women in both early and then late gestation and women with diagnosed pregnancy-induced hypertension (PIH). Blood was collected from each subject for estimation of plasma angiotensin II concentration and isolation of platelets, which were then used in non-competitive binding studies. Both receptor capacity and affinity for the ligand were calculated for each subject. In the control group, a significant negative correlation between angiotensin II and receptor capacity was established. This was in marked contrast to the first trimester group which showed no such correlation and where there was a significant reduction or nil receptor capacity but only a slight elevation in mean plasma angiotensin II concentration. This phenomenon of reduced or absent binding persisted into the third trimester when plasma angiotensin II was significantly elevated compared with all other groups. PIH subjects had the lowest plasma angiotensin levels and 90% had clearly measurable binding to the platelet receptor, which was not however as high as that in the control group. Two normotensive subjects who demonstrated significant potentiation of receptor binding in the third trimester subsequently developed PIH. The inverse relation between plasma angiotensin II and its platelet receptor, found in non-pregnant subjects, is significantly altered in normal pregnancy. Reduced receptor capacity and lack of relation with circulating ligand observed in early gestation reflects an alteration at the receptor level which is independent of plasma angiotensin II concentration. This alteration appears to persist throughout pregnancy except in subjects predisposed to PIH when receptor binding is closer to non-pregnant values. Changes in receptor binding found in people who ultimately developed PIH but who were still clinically normal at the time suggest that binding to the platelet receptor could be used as a screening test for all primiparae to identify those predisposed to PIH later on in pregnancy.

GASTRIC EMPTYING IN PREGNANCY

The rate of gastric emptying in pregnancy was measured indirectly using the rate of paracetamol absorption in four groups of 15 patients: non-pregnant controls, first trimester patients presenting for termination of pregnancy, second trimester patients presenting for prostaglandin termination of pregnancy, and patients presenting for elective Caesarean section. All patients were fasted for 6 h and then received paracetamol tablets 1.5 g orally with water 50 ml. Blood samples were taken at 15-min intervals for 120 min and analysed for paracetamol concentration. There was no significant difference between the groups in the maximum concentration and time to maximum concentration (ANOVA). The AUC was reduced for the first trimester group at 60 and 120 min (P less than 0.05). No significant delay in gastric emptying was demonstrated in any of the three trimesters of pregnancy compared with the control group.

Effects of supine exercise on fetal heart rate in the second and third trimesters.

The effects of a brief period of supine exercise on fetal heart rate (FHR) was studied in 25 healthy, regularly exercising women, 12 in the late second trimester and 13 in the mid third trimester. Although statistically significant increases in maternal mean arterial pressure and pulse occurred, the exercise intensity was mild, with the average percent maximal pulse being 46 +/- 5% and 49 +/- 5% in the second and third trimester groups, respectively. Small increases in FHR were seen in both groups, which were insignificant statistically and physiologically. No patient experienced significant FHR abnormalities as a result of the supine exercise sequence. The findings suggest that pregnant women may continue submaximal supine exercise of short duration into the mid to late third trimester.

Nausea and vomiting in pregnancy.

Prospective data on 86 pregnant women were analysed to investigate the relationship between the pregnancy symptoms of nausea and vomiting and various demographic, social and psychological factors. In contrast to previous research findings no significant differences were discovered along demographic or social dimensions between women reporting no nausea, mild nausea and severe nausea during the first trimester of pregnancy. Not surprisingly, those women experiencing severe nausea reported significantly more sleep disturbances, fatigue and irritability. Women having both nausea and vomiting during the first trimester, reported significantly more unplanned, undesired pregnancies and negative relationships with their own mothers, than first trimester groups experiencing nausea only or no symptoms. Finally, those with continuing nausea and vomiting in the third trimester, when compared with those having no symptoms, tended to have reported significantly more psychological/psychiatric problems in the first trimester and were significantly more negative in their assessment of their own maternal relationship.