Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases

BackgroundPreeclampsia is a pregnancy specific disorder affecting 3–5% of pregnancies worldwide. It is clinically divided into early-onset and late-onset subtypes. Placental factors are involved in the pathogenesis of preeclampsia. Growth differentiation factor 15 (GDF15), a protein of the transforming growth factor beta superfamily, is highly expressed in the placenta. However, it is unclear whether the circulating levels of GDF15 are altered in preeclampsia at the time of or prior to disease presentation.MethodsSerum samples across three trimesters from 29 healthy pregnancies, third trimester sera from 34 women presenting with preeclampsia (early-onset n = 16, late-onset n = 18) and 66 gestation-age-matched controls, and sera at 11–13 weeks of pregnancy from women who later did (n = 36) or did not (n = 33) develop late-onset preeclampsia, were examined for GDF15 by ELISA.ResultsSerum GDF15 levels increased significantly with gestation in normal pregnancy. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia compared to their gestation-age-matched controls. This reduction was apparent in both early-onset and late-onset subtypes, but it was more profound in late-onset cases. At 11–13 weeks of gestation, however, serum levels of GDF15 were similar between women who subsequently did and did not develop late-onset preeclampsia.ConclusionSerum GDF15 increased with gestation age, reaching the highest level in the third trimester. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia, especially in late-onset cases. However, serum GDF15 was not altered in the first trimester in women destined to develop late-onset preeclampsia.     

Stillbirth as risk factor for depression and anxiety in the subsequent pregnancy: cohort study

ObjectiveTo assess women’s symptoms of depression and anxiety during pregnancy and the postpartum year in the pregnancy after stillbirth; to assess relevance of time since loss.DesignCohort study with four assessments: in third trimester and 6 weeks, 6 months, and 12 months after birth.SettingOutpatient departments of three district general hospitals; subjects’ homes.Subjects60 women whose previous pregnancy ended in stillbirth after 18 weeks’ gestation; 60 matched controls.ResultsIn the third trimester women whose previous pregnancy had ended in stillbirth were significantly more depressed than control women (10.8 v 8.2; P=0.004) and had greater state anxiety (39.8 v 32.8, P=0.003) The difference was accounted for by those women who conceived less than 12 months after the stillbirth, who were also more depressed at 1 year. Results in those who conceived 12 months or more after stillbirth were similar to those in their controls at all points and showed lower trait anxiety 1 year post partum. One year after the birth 8% of control women and 19% of subjects scored high for depression (P=0.39), with most of the depression among the more recently bereaved (28% v 11%; P=0.18). In the women who had experienced stillbirth, depression in the third trimester was highly predictive of depression 1 year after subsequent birth (P⩽0.0005).ConclusionVulnerability to depression and anxiety in the next pregnancy and puerperium is related to time since stillbirth, with more recently bereaved women at significantly greater risk than controls. As there are problems for mother and infant associated with high anxiety and depression during and after pregnancy, there may be advantage in waiting 12 months before the next conception.

Key messages

• Women whose previous pregnancy ended in stillbirth had significantly higher levels of depression and state anxiety during their subsequent pregnancy than matched controls
• Those who had conceived over 12 months after stillbirth were, however, similar to controls at all points and had lower trait anxiety a year after the next birth
• Women who had conceived within 12 months after loss had a significantly higher risk of high state anxiety during the next pregnancy and of depression and both state and trait anxiety 12 months post partum than women with longer time since loss
• Women may need a year to mourn the lost child before beginning another pregnancy or women who chose to conceive sooner may be intrinsically more vulnerable to depression and anxiety
• Parents have various and individual reasons for timing the next pregnancy, but there may be advantage in waiting 12 months before conception

     

Comparison of child-rearing problems between mothers with multiple children who conceived after infertility treatment and mothers with multiple children who conceived spontaneously.

The purpose of this study was to clarify the characteristic child-rearing problems for mothers of multiple children who conceived after infertility treatment as compared to mothers of multiple children who conceived spontaneously. The subjects were 990 mothers of multiple children: 359 who conceived after infertility treatment and 631 who conceived spontaneously. Mothers who conceived after infertility treatment were more delighted when informed of a multiple pregnancy than those who conceived spontaneously. In addition, with respect to anxiety during twin pregnancies, mothers of twins who conceived after infertility treatment showed lower rates of anxiety about nursing the infants and economic concerns than those of twins who conceived spontaneously. However, after delivery, mothers who conceived after infertility treatment showed a higher rate of depressive symptoms than those who conceived spontaneously. After adjusting for each associated factor using logistic regression, the risk of depressive symptoms in mothers who conceived after infertility treatment was significantly associated with disabled multiple children and the methods for alleviating stress. The odds ratio indicated that mothers with at least one disabled child were twice as likely to have depressive symptoms as mothers with no disabled children. Furthermore, the odds ratio indicated that mothers who used no methods for alleviating stress were twice as likely to have depressive symptoms than those who did.     

Pregnancy,prolactin, and pituitary tumours

Nine pregnancies are described in patients with pituitary tumours. All patients had definite radiological evidence of a pituitary tumour and no evidence of acromegaly or Cushing''s disease. In seven patients serum prolactin levels were estimated before pregnancy and found to be raised.Seven patients had been treated with pituitary implantation of yttrium-90. The remaining two developed complications of the tumour during pregnancy. One developed a bitemporal visual field defect in the second trimester which was successfully treated by emergency yttrium-90 implantation. The other developed diabetes insipidus in the third trimester which resolved spontaneously after delivery.Six patients were treated with drugs to achieve pregnancy. Four took bromocriptine to suppress raised prolactin levels, one was treated with human menopausal gonadotrophin, and one was treated with clomiphene.     

Nominations sought for Mindel C. Sheps Award

Abstract

The relationship between early fetal wastage or stillbirth and pregnancy spacing was examined in a population characterized by prolonged lactation, minimal nutrition, and high fertility and mortality. The highest risk of early fetal death was found among those pregnancies conceived less than twelve months after the birth of a surviving breast‐fed infant. Lactation as a possible causal factor is discussed. A significant inverse relationship was apparent for second trimester fetal deaths and pregnancy intervals, but not for third trimester deaths. This finding is surprising when one considers that fetal weight gain, and presumably nutrient demand, increases most rapidly during the third trimester.     

Influence of serum luteinising hormone concentrations on ovulation,conception, and early pregnancy loss in polycystic ovary syndrome.

Women with the polycystic ovary syndrome do not respond well to treatment with luteinising hormone releasing hormone. To determine whether this might be due to an underlying endocrine disturbance basal concentrations of luteinising hormone were measured in 54 infertile women treated with pulsatile luteinising hormone releasing hormone and concentrations at the time of maximum follicular growth were measured in 23 of the patients. Forty one patients ovulated. Forty one patients ovulated and 27 conceived, but nine pregnancies terminated within four weeks after ovulation. Basal luteinising hormone concentrations were significantly lower in those who conceived (12.4 (range 1.3-29.0) IU/l) than in those who did not (19.0 (3.5-50.0) IU/l) and in those whose pregnancy progressed (9.6 (1.3-29.0) IU/l) than in those with early loss of pregnancy (17.9 (7.0-29.0) IU/l). Concentrations at the time of maximum follicular growth were significantly lower in women who ovulated (9.4 (2.9-35.4) IU/l) than in those who did not (29.0 (7.0-50.0) IU/l) and in those who conceived (6.2 (2.9-8.5) IU/l) than in those who did not (17.9 (4.0-50.0) IU/l). These results indicate that high concentrations of luteinising hormone during the follicular phase in women with polycystic ovaries have a deleterious effect on rates of conception and may be a causal factor in early pregnancy loss.     

Pregnancy in patients presenting with hyperprolactinaemia.

Ninety-two pregnancies occurred in 76 hyperprolactinaemic patients treated with bromocriptine. Half conceived within three months of attempted conception. There was no evidence of an increased rate of spontaneous abortion, fetal abnormality, or multiple pregnancy; the three twin pregnancies occurred in women who were additionally treated with clomiphene and human chorionic gonadotrophin. Thirty-one patients had radiological evidence of a pituitary tumour; 14 with major radiograph changes in the pituitary fossa or serum prolactin concentrations greater than 100 ng/ml received pituitary irradiation before conception. None of the latter showed evidence of enlargement of the tumour during pregnancy. In contrast two of the four patients with similar tumours but who were not irradiated developed visual field defects, one with gross destruction of the pituitary fossa. Prophylactic treatment to limit subsequent tumour expansion during pregnancy in patients with prolactinomas is indicated, and pituitary irradiation before conception appears to be a safe and effective method to achieve this goal.     

Urine Selenium Changes During Pregnancy Do Not Correlate with Thyroid Autoantibodies in a Mildly Iodine Deficient Population

Selenium (Se) is a key component of iodinases; higher Se levels are associated with lower titers of antithyroid peroxidase antibodies (anti-TPO). Pregnancy exerts profound effects on thyroid function and autoimmunity. To assess the relationship of urine Se levels with thyroid function and autoimmunity in pregnant women residing in Athens, Greece, we studied prospectively 47 euthyroid women in uncomplicated singleton pregnancies (mean age + SD: 30?+?5 years) in each trimester, measuring urine Se levels, urine iodine, plasma thyrotropin (TSH), free thyroxine and triiodothyronine (FT4 and FT3), as well as levels of anti-TPO antibodies. Changes of the measured parameters were assessed over each trimester; thyroid parameters were assessed with relation to Se levels. Urine Se dropped by the third trimester, whereas urine iodine did not change appreciably during pregnancy. TSH and anti-TPO did not show appreciable changes; FT4 and FT3 gradually decreased as the pregnancy advanced. No relationship between urine Se levels and anti-TPO was found. During pregnancy, changes in urine Se levels accompany mild changes in thyroid function. However, we did not find some association between these changes and thyroid autoimmune activity over this period, probably because the effect of Se on thyroid autoimmunity may only become apparent in case of excess Se fortification.     

Effect of pregnancy on serum cytokines in SLE patients

Introduction

The aim of this study was to evaluate an extensive panel of cytokines involved in immune regulation during pregnancy in patients with systemic lupus erythematosus (SLE) and in healthy women.

Methods

A total of 47 consecutive successful pregnancies in 46 SLE patients and 56 pregnancies in 56 matched healthy subjects, as controls, were prospectively studied. Serum interleukin (IL)-1-α, IL-1-β, IL-2, IL-6, IL-8, IL-10, IL-12p70, interferon (INF)-γ and tumor necrosis factor (TNF)-α were detected in sera obtained at the first and third trimester of pregnancy by a highly sensitive, multiplexed sandwich ELISA.

Results

Medians (pg/ml) of serum levels of most helper T (Th)1-type cytokines were significantly lower in the third trimester compared with those observed in the first trimester of pregnancy in healthy women: INF-γ 2.0 vs 3.4, TNF-α 10.2 vs 11.5, IL-1-α 0.9 vs 1.1, IL-1-β 0.6 vs 1.0, IL-2 3.0 vs 3.5, and IL-12p70 4.9 vs 5.6 (P-values < 0.02 for all). By contrast, only the IL-1-α serum levels were lower in the third trimester compared with the first trimester in SLE patients (P = 0.006). IFN-γ/IL-6 and IFN-γ/IL-10 ratios were higher in controls than in SLE (P = 0.002, and P = 0.001, respectively); moreover, they were significantly reduced in the third compared to the first trimester of pregnancy in healthy women, but not in SLE.

Conclusions

In SLE patients, Th1/Th2 cytokine serum level ratio does not decrease during pregnancy progression as much as in healthy pregnant women. This could account for the observation of a low frequency of disease flares in the third trimester of gestation.     

Increased risk of recurrence of pregnancies complicated by fetal neural tube defects in mothers receiving poor diets,and possible benefit of dietary counselling.

One hundred and seventy-four women who had previously had a child with a neural-tube defect were assessed retrospectively on the quality of their diets during the first trimester of that pregnancy, between pregnancies, and during the first trimester of other pregnancies. They were then studied prospectively during the first trimester of 186 following pregnancies and the outcome of these was recorded. One hundred and three women (with 109 pregnancies) were given dietary counselling before the pregnancy, the remaining 71 (with 77 pregnancies) not being counselled. Seventy-eight (72%) of the counselled women improved their diet compared with only nine (12%) of the uncounselled women. The difference was significant (p < 0.001). There were three recurrences of neural-tube defects in the counselled women (3%) and five recurrences in the uncounselled (7%). Although this difference was not significant, the relative risk in the counselled group was reduced to less than half of that in the uncounselled group. All eight recurrences occurred in the 45 pregnancies in women taking poor diets (18%), whereas there were no recurrences in the 141 other pregnancies. This difference is significant (p < 0.001). It is concluded that women receiving adequate diets have a lower incidence and recurrence of fetal neural-tube defects than women receiving poor diets and that dietary counselling may be effective in reducing the incidence of fetal neural-tube defects.     

Iodine in early pregnancy--is there enough?

Aims: To evaluate the iodine status of patients in early pregnancy and its dependence on level of thyroid-stimulating hormone (TSH). Methods: Between June 2005 and December 2006, 168 patients with a confirmed vital pregnancy (up to 10(th) week of pregnancy) were included in the study. The entry criteria were no prior thyroid disease, did not take any other medication, had not undergone radio-iodine therapy and did not take multivitamins containing iodine. The iodine status was measured as the amount of iodine in urine over 24 hours. The TSH level was determined from the blood using chemiluminescence. Results: The average ioduria value in patients was found to be 3.04 micromol/24 hr, with the norm 0.6-2.4 micromol/ 24 hr, median 2.9, SD 1.5. None of the patients had a value lower than 0.9 micromol/24 hr. The average TSH value was 1.98 mIU/l, median was 1.31, SD 0.98. The laboratory limits were set to 0.25-3 mIU/l for pregnant women in the first trimester. Three pregnancies ended in miscarriage by week 12, 1 miscarriage occurred in week 22 and the other pregnancies concluded in delivery between weeks 38-41. Fourteen patients had TSH levels above 3 mIU/l with normal levels od free thyroxine (T4) : 10.3-25 pmol/l. Conclusions: The results of this study did not reveal any iodine deficit in any of the patients. However 14 patients had elevated TSH levels signalling subclinical or incipiently clinical hypothyroidism. These pacients underwent levothyroxine therapy after endocrinologist's consultations.     

Posthemithyroidectomy Pregnancy Thyroid Function Surveillance: Frequency,Adherence, and Guideline Impact

ObjectivePosthemithyroidectomy women are at an increased risk for gestational subclinical hypothyroidism. Therefore, the American Thyroid Association (ATA) recommends increased thyroid function surveillance for this subgroup of pregnant women. The purpose of this study was to evaluate the frequency of thyroid function surveillance during pregnancy in posthemithyroidectomy women and to evaluate the adherence to the 2017 ATA guidelines and its possible impact since being published on thyroid function surveillance rates.MethodsA retrospective study of pregnant posthemithyroidectomy women operated at our institution between 1997 and 2020 was performed. The study cohort was subdivided by pregnancy dates before 2018 and 2018 onward to evaluate the impact of the 2017 ATA guidelines. Adherence to the guidelines was defined as at least 1 thyroid-stimulating hormone test in each trimester.ResultsAfter exclusions, a total of 120 pregnancies conceived by 66 women who underwent hemithyroidectomy surgeries were included in this study. Overall, serum thyroid-stimulating hormone examinations were performed during the first, second, and third pregnancy trimesters in 86.6%, 40%, and 16.6% of pregnancies, respectively (P <.005). The examination rate since 2018 was 88%, 40%, and 8% for the first, second, and third trimesters, respectively (P <.005).ConclusionAdherence to the latest ATA guidelines is low, and its publication in 2017 did not increase the thyroid function surveillance rate in posthemithyroidectomy women. Better patient education regarding the risks of gestational hypothyroidism following hemithyroidectomy and improved communications among treating surgeons, obstetricians, and endocrinologists may improve these rates.     

Self-monitoring of blood glucose in diabetic pregnancy.

Admission to hospital is usually recommended to achieve the best possible diabetic control during pregnancy. We have used blood glucose monitoring at home to find out if patients can achieve equally good control outside hospital. Twenty-five consecutive diabetic patients were studied, of whom 20 had taken insulin before pregnancy. Six of their 14 previous pregnancies had ended in perinatal death. The 25 women performed 4247 blood glucose measurements during their pregnancies. Overall the mean blood glucose concentration was 7.1 mmol/l (128 mg/100 ml); before meals the mean was 6.5 mmol/l (117 mg/100 ml). Mean concentrations were lower in the third trimester, but at no stage was control in hospital significantly better than at home. The mean hospital stay before delivery was 22 days, and all patients had live babies. Monitoring blood glucose concentrations at home produces greater understanding and motivation among patients, improves control early in pregnancy, and shortens time spent in hospital.     

Serum concentrations of androstenediol and androstenediol sulfate, and their relation to cytokine production during and after normal pregnancy

Since it is known that androstenediol (ADIOL) has potent immunoregulatory effects, changes in ADIOL levels during and after pregnancy might affect the maternal immune system. We examined serum concentrations of ADIOL and androstenediol 3-sulfate (ADIOLS) together with IFN-gamma and IL-4 production levels during pregnancy and after delivery up to 10-11 months postpartum. The subjects were 73 normal pregnant, 76 normal postpartum, and 28 normal non-pregnant women. ADIOL and ADIOLS were measured using EIA and GC/MS, respectively. The cytokine levels in the supernatant of whole-blood cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin were measured using ELISA. ADIOL levels significantly decreased compared to non-pregnant levels in the first trimester (P < 0.05) and were reversed in the third trimester (P < 0.05). After pregnancy, ADIOL levels gradually declined, and a significant decrease was observed at 10-11 months postpartum (P < 0.05). ADIOLS levels were significantly lower in the third trimester (P < 0.05) and significantly higher at the first month postpartum (P < 0.001) compared to non-pregnant women. IFN-gamma and IL-4 levels decreased during pregnancy and subsequently increased postpartum. On the other hand, we found significant negative correlations between ADIOL concentrations and production levels of IFN-gamma (P < 0.05) or IL-4 (P < 0.05). These findings suggest that ADIOL may be involved in modifying the maternal immune response during and after pregnancy.     

Effects of legal termination on subsequent pregnancy.

Two hundred and eleven patients who had undergone vaginal termination and were pregnant again were investigated; 43-2% had become pregnant within one year of termination. The overall fetal loss in the 211 patients was 17-5% compared with 7-5% in a group matched for parity but consisting of patients who were pregnant after a spontaneous abortion. Altogether 4-3% of pregnancies after legal abortion ended as first trimester abortions, 8-5% as second trimester abortions, and 13-7% in premature delivery. Among 11 women whose cervices had been lacerated at the time of legal termination the fetal loss in subsequent pregnancy was 45-5%, and only one pregnancy went beyond 36 weeks. Routine Shirodkar suture may be beneficial when the cervix is known to have been damaged at legal abortion. Several patients had asked that their general practitioner should not be told of their termination, and such patients may not admit their termination during a subsequent pregnancy, which could thus be jeopardised. No evidence was found to suggest that infants of patients with a history of legal termination are small for dates.     

A longitudinal study of free leptin index in pre-eclamptic pregnancies

The ratio between circulating levels of leptin and soluble leptin receptor (sOB-R), the free leptin index (FLI), is used as a marker of leptin resistance. Therefore, the aim of our study was to investigate the FLI in mild pre-eclamptic pregnancies in a nested case–control study within a prospective observational study. Circulating levels of leptin and sOB-R levels rise significantly during pregnancy in healthy (p < 0.05) (n = 46) and pre-eclamptic pregnancies (p < 0.05) (n = 20). Serum levels of leptin were significantly higher in pre-eclamptic compared to healthy pregnancies at second and third trimesters of pregnancy (p < 0.05). Additionally, serum levels of sOB-R were significantly lower in pre-eclamptic pregnancies during the second and third trimesters of pregnancy compared to healthy pregnancies (p < 0.05). Moreover, we found that FLI did not vary significantly during pregnancy in healthy women (p > 0.05), while it increases in pre-eclamptic pregnancies (p < 0.05). Indeed, FLI was significantly higher at second and third trimesters of pregnancy in pre-eclamptic compared to healthy pregnancies (p < 0.05). In addition, FLI was significantly higher in the luteal phase compared with the follicular phase of the menstrual cycle in eumenorrheic women (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed the ability of leptin (AUC = 0.72) and FLI (AUC = 0.67) as a reliable predictor for mild pre-eclampsia during the second trimester of pregnancy. In conclusion, our findings show that FLI were significantly increased in mild pre-eclamptic pregnancies and allowed us to hypothesize that this rise might alter leptin bioavailability and bioactivity which might lead to the sympathetic hyperactivity and the hypertensive disorders during pregnancy.     

Selenium and malondialdehyde content and glutathione peroxidase activity in maternal and umbilical cord blood and amniotic fluid

Placenta tissue may be a major source of lipid peroxidation products in pregnancy. It was proven that placental peroxidation activity increases with gestation. Selenium (Se), as an essential constituent of glutathione peroxidase (GSH-Px), takes part in the reduction of hydrogen peroxides and lipid peroxides. Malondialdehyde (MDA) is a major breakdown product split off from lipid peroxides. In this study, Se and MDA content and GSH-Px activity were measured in blood and plasma taken from 20 apparently healthy nonpregnant women between 19 and 38 yr of age and from 115 unselected pregnant women between 17 and 45 yr of age (35 in the first trimester, 22 in the second trimester, 38 in the third trimester, and 20 within 2 d of delivery). Samples of umbilical cord blood and amniotic fluid were taken from women in the second and third trimesters and at delivery. The Se content was measured by atomic absorption spectrometry (AAS), plasma MDA concentration by thiobarbituric acid reaction, and Se-dependent GSH-Px spectrometrically. Blood and plasma Se contents of nonpregnant women were below those considered adequate, indicating low selenium intake. In comparison to nonpregnant women, pregnant women had significantly decreased whole-blood and plasma Se levels in the second and third trimesters and at delivery. The significant drop of whole-blood SeGSH-Px activity was observed in the first trimester of pregnancy and its lower activity was maintained until delivery. A significant drop in plasma SeGSH-Px activity occurred in the second trimester and attained the minimal level at delivery. The Se level and SeGSH-Px activity in maternal and umbilical cord blood were at similar levels. Amniotic-fluid SeGSH-Px activity was nondetectable or exceptionally low and its Se content remained unchanged during pregnancy. Plasma levels of MDA were significantly decreased in the second and third trimesters and at delivery. The fetal blood plasma at birth had a lower MDA level compared to the levels of MDA of their mothers at delivery. A low, but significant inverse correlation existed between blood SeGSH-Px activity and plasma MDA content and between plasma Se and plasma MDA contents during pregnancy. A significant decrease of Se and SeGSH-Px activities (antioxidant enzyme) in both blood and plasma suggests a possible drop in total antioxidant status during pregnancy. Elevated MDA plasma levels might be the result of increased lipid peroxidation in placental tissue during pregnancy.     

Maternal age, gravidity, and pregnancy spacing effects on spontaneous fetal mortality

Differentials in the probability of pregnancy loss are examined using pregnancy history data from eight WFS surveys in developing countries. Multiple logistic regression equations are estimated. The probability of loss varies substantially over the reproductive career. Both higher-order pregnancies and those conceived at older ages are more likely to terminate in loss. maternal age differentials are more pronounced for lower-order pregnancies. First and second pregnancies conceived over age thirty suffer especially high levels of loss. Pregnancies conceived relatively soon after the termination of the previous pregnancy are more likely to be lost, as are pregnancies conceived after long intervals. Risk of loss is higher for women previously experiencing loss, and the effect persists beyond the pregnancy following the loss.     

Accuracy of mothers' retrospective reports of smoking during pregnancy: comparison with twin sister informant ratings.

Retrospective assessment of maternal smoking or substance use during pregnancy is sometimes unavoidable. The unusually close relationship of twin sister pairs permits comparison of self-report data versus co-twin informant data on substance use during pregnancy. Information about smoking during pregnancy has been gathered from a series of mothers from an Australian volunteer twin panel (576 women reporting on 995 pregnancies), supplemented in many cases by independent ratings of their smoking by twin sister informants (821 pregnancies). Estimates of the proportion of women who had never smoked regularly (56-58%), who had smoked but did not smoke during a particular pregnancy (16-21%), or who smoked throughout the pregnancy (16-18%), were in good agreement whether based on self-report or twin sister informant data. However, informants underreported cases who smoked during the first trimester but then quit (1-3% versus 7-9% by self-report). Women who smoked throughout pregnancy (by informant report) rarely denied a history of regular smoking (< 1%), although a small proportion of apparent false negative cases were identified where they either denied smoking during a pregnancy (9%) or denied smoking beyond the first trimester (10%). We conclude that retrospective smoking data can safely be used to identify potential associations of later child outcomes with maternal smoking during pregnancy.     

First-trimester NRBC count in maternal circulation: correlation with doppler ultrasound studies.

This study aimed to determine whether the number of nucleated red blood cells (NRBCs) in maternal circulation during the first trimester of pregnancy could identify pregnancies that will have an anomalous Doppler in the second trimester. A total of 85 blood samples were obtained at 11-14 weeks of gestation with mean uterine arterial perfusion index >1.6, as noted by Doppler ultrasonography. NRBCs were enriched by magnetic automated cell sorting using anti-CD71 and were stained with May/Grunwald/Giemsa. A total of 4.8 NRBCs (range 1-75) were identified in 68 cases. Follow-up scans at 22-24 weeks were available in 46 cases. In 39 women, blood flow in the uterine arteries normalized, whereas in seven, high resistance was noted. One woman in the high-resistance group developed preeclampsia (PET; four NRBCs) and another delivered an intrauterine growth restriction (IUGR) baby (75 NRBCs). The number of NRBCs in women whose Doppler indices later normalized and in those who continued to have increased impedance was similar. The study indicates that NRBC number in maternal circulation during the first trimester cannot be used to screen pregnancies at high risk for developing preeclampsia (PET)/IUGR. High-impedance blood flow in the uterine arteries in the first trimester may be due to an unfinished process of trophoblastic invasion, most likely to be completed successfully by 22-24 weeks.