Early Puerperium Research Articles

Immune activation in the early puerperium is related to postpartum anxiety and depressive symptoms

The pathophysiology of the postpartum blues, common transient mood disorders in the first week postpartum, has remained elusive. Recently, however, it has been shown that depression and anxiety disorders are accompanied by activation of the inflammatory response system (IRS). This study was developed to determine whether the postnatal blues is associated with IRS activation. Serum concentrations of interleukin-6 (IL-6), IL-6 receptor (IL-6R), gp130 (the IL-6 signaling protein), IL-1R antagonist (IL-1RA) and leukemia inhibitory factor receptor (LIFR) were assayed in 22 nonpregnant women and in 91 pregnant women before delivery and 1 and 3 days after delivery. On each occasion the parturient women completed the State version of the Spielberger State-Trait-Anxiety-Inventory (STAI) and the Zung Depression Rating Scale (ZDS). Serum IL-6, IL-1RA and LIFR were significantly higher in pregnant women at the end of term than in nonpregnant women.

Effects of pregnancy and delivery on serum concentrations of Clara Cell Protein (CC16), an endogenous anticytokine: lower serum CC16 is related to postpartum depression

There is now some evidence that lower serum concentrations of Clara Cell Protein (CC16) are related to stress-induced anxiety, psychoses and major depression. This study was developed to determine whether serum CC16 is lowered in the early puerperium and whether Postnatal Depression and Postnatal Blues are associated with lower levels of serum CC16. Serum concentrations of CC16 were assayed in 17 non-pregnant women and in 98 pregnant women before delivery and 1 and 3 days after delivery. On each occasion the parturients completed the State version of the Spielberger State-Trait Anxiety Inventory (STAI) and the Zung Depression Rating Scale (ZDS). Serum CC16 was significantly lower in pregnant women, at the end of pregnancy as well as 1 and 3 days after delivery, than in the non-pregnant women. Serum CC16 was somewhat, although significantly, higher 1 and 3 days after delivery than before delivery. Parturients who developed a postpartum depression had significantly lower serum CC16 concentrations than women who did not. There were no significant differences in serum CC16 between the puerperal women whose STAI or ZDS scores increased in the puerperium and those whose scores did not. It is concluded that in puerperal women there is a decreased anti-inflammatory capacity in the serum, in part caused by lowered serum CC16, and that the latter may be related to the development of postpartum depression.

Uterine Motility in the Cow During Puerperium

SummaryThe objective of the study was to determine uterine motility during the postpartum period in cattle. In the present study spontaneous uterine activity was recorded during postpartum period using electrodes which were surgically implanted into the myometrium 4‐6 weeks before parturition. After the placenta has been released 4‐8 hours post part, spontaneous uterine motility drastically decreased until the second week post part. The effects of oxytocin, depotocin, prostaglandin, ergometrin, detomidin on the uterine contractility, during postpartum period were investigated. Oxytocin and carbotocin given intravenously always provoked strong uterine contractions. Prostaglandin F2alpha and detomidinum HC1 stimulated uterine activity in the early puerperium. Following administration of ergometrin unequal response was recorded. Ultrasonographic examinations were performed daily with real time B‐mode scanner equipped with a 5.0 MHz linear‐array transducer (Aloka 210, Pie Medical). 10 muciparous Black‐White‐Holstein cows between 2 and 4 years old and 550‐650 kg b.w. were used. A 6‐min scan of the longitudinal view of the uterine body was recorded using video cassette recorder connected to the ultrasound scanner. A scoring system was used to determines uterine motility. Contractility scores were higher just after parturition then in the following times. Blood samples were collected daily from jugular vein for plasma progesterone and estrogen concentrations. Changes in uterine activity were associated with plasma progesterone and estrogen level.

Postpartum dysphoric syndrome. Psychopathology, diagnosis and etiology

About half of newly delivered mothers suffer a transient phase of emotional lability or sadness a few days after parturition around the 2nd and 5th day after delivery. The transitory psychopathology of the postpartum blues is similar to premenstrual tension, whose main symptom is irritability. The essence of the postpartum blues is not depression, but a sudden, fleeting and unexpected mood change with anxiousness, low spirits, tearfulness, confusion, poor concentration and forgetfulness. The aetiology of this disorder is unknown. It is well known that oestrogens and progesterone modify catecholamine concentration and the density of adrenergic, noradrenergic und dopaminergic receptors in the limbic structures of the central nervous system. But most of the neurochemical studies have not distinguished between postpartum blues and other forms of depression found in women and occurring postpartum. Those research groups who defined a group with a dysphoric peak in the early puerperium could not find a significant correlation between sex hormone levels, neurobiochemical data, and postpartum mood changes.

A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy.

Maternal serum concentrations of inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC-related inhibin forms, total follistatin, steroids and gonadotrophins were measured longitudinally in six normal singleton pregnancies. Maternal venous blood was collected randomly during a spontaneous follicular phase prior to donor insemination, at 5, 7, 9, 11, 16, 20, 24, 28, 32 and 36 weeks after the first missed menses and in the early puerperium. Steroid and gonadotrophin profiles conformed to previous reports. While at week 5 of gestation inhibin-A, activin-A and follistatin concentrations were similar to those at the follicular phase, all three increased progressively (P < 0.001) to maximal concentrations in week 36: approximately 48-fold (3740 +/- 1349 ng inhibin-A/ml), approximately 22-fold (6109 +/- 1443 ng activin-A/ml) and approximately 10-fold (3563 +/- 418 ng follistatin/ml) higher. Pro-alphaC concentrations reached a maximum in weeks 5 (approximately 5-fold, P < 0.001) and 36 (1027 +/- 174 pg/ml, P < 0.01). Inhibin-B (71 +/- 23 pg/ml prior to pregnancy) was undetectable (<12 pg/ml) between week 5-16 of gestation but increased slightly in the third trimester (26 +/- 7 pg/ml in week 36). Activin-AB was undetectable throughout pregnancy. Post-partum concentrations of inhibin-A (41 +/- 12 ng/ml), inhibin-B (<12 pg/ml), activin-A (950 +/- 149 pg/ml), pro-alphaC (128 +/- 22 pg/ml) and follistatin (990 +/- 79 ng/ml) were substantially lower than at week 36 of gestation. The activin-A:follistatin ratio increased from 0.5 in week 5 to 1.8 in week 36, suggesting that more free activin-A is available in the maternal circulation during late pregnancy.

Endothelial Cell Markers and Fibrinopeptide A to D-Dimer Ratio as a Measure of Coagulation and Fibrinolysis Balance in Normal Pregnancy

Objective: Changes in hemostatic system were evaluated in healthy pregnant women. Methods: Blood was sampled in the 1st, 2nd and 3rd trimesters of gestation, during delivery and 3 days postpartum and plasma factors were measured using commercial tests. Results: Thrombin-antithrombin III complexes, fibrinopeptide A and D-dimer were higher during pregnancy. The endothelial cell markers, fibronectin and tissue factor, remained within the normal reference values in the healthy nonpregnant population. This result suggests no endothelial injury and shows no activation of extrinsic coagulation pathway during pregnancy. The balance coagulation/fibrinolysy is maintained during pregnancy and delivery, as shown by the ratio fibrinopeptide A/D-dimer, however, a tendency towards coagulation process is developed in the early puerperium.

Transfer from home to hospital: what is its effect on the experience of childbirth?

In the Netherlands women with low-risk pregnancies are free to choose where to give birth, at home or in hospital, attended by an independent midwife or general practitioner. On average one of five women who remains in the care of a midwife at the onset of labor will be referred to an obstetrician during or shortly after childbirth. If women had planned to give birth at home, they would then have to be transferred to the hospital. Postal questionnaires were sent to 2301 pregnant women before and after birth to measure the experience of childbirth, appropriateness of the chosen place of birth, satisfaction with the birth, midwife's care, and first days postpartum of women planning to give birth at home or in hospital. The response rate for both questionnaires was 89.3 percent. Of 745 nulliparous women and 895 multiparous women, 39.3 and 10.3 percent, respectively, experienced referral to an obstetrician during labor. Of these women, the ones who wanted to give birth at home but were transferred to hospital because of the referral were as positive about the birth, early puerperium, and attendance of the midwife as the women who wanted to give birth in hospital. Our research showed, contrary to expectations, that an unplanned transfer from a planned home birth to hospital has little influence on the experience of childbirth.

Circulating endothelin-3 and prolactin concentrations in healthy lactating women during the early puerperium.

To study the association between the circulating concentrations of endothelin-3 and prolactin in the early puerperium. Prospective clinical study, including twenty-five healthy puerperal women breast-feeding their healthy full-term infants. Venous blood was drawn on day 1 and 4 post partum, and plasma endothelin-3 and serum prolactin were determined. Circulating endothelin-3 and prolactin levels on day 4 did not differ significantly from the corresponding levels on day 1. However, a significant negative correlation was found on day 4 between endothelin-3 and prolactin values (r = -0.688, P < 0.001) and an even stronger negative association existed between the net change in endothelin-3 from days 1 to 4 and the corresponding change in prolactin values (r = -0.732, P < 0.001). On the fourth day post partum, lactating healthy women show negative correlation between circulating endothelin-3 and prolactin levels. Whether this indicates a role for endothelin-3 in the control of prolactin secretion in the post partum period remains to be clarified.

Activated Protein C Sensitivity, Protein C, Protein S and Coagulation in Normal Pregnancy

A prospective study of activated protein C sensitivity, protein C, protein S, and other coagulation factors in 239 women during normal pregnancy was carried out. Protein C activity appeared unaffected by gestation, although an elevation of protein C activity was observed in the early puerperium. A fall in total and free protein S with increasing gestation was observed. Activated protein C sensitivity ratio (APC:SR) showed a progressive fall through pregnancy. This fall correlated with changes in factor VIIIc, factor Vc and protein S. 38% of subjects, with no evidence of Factor V Leiden or anticardiolipin antibodies, showed a low APC:SR (APC:SR <2.6) in the third trimester of pregnancy. Aside from a significant reduction in birth weight, no difference in pregnancy outcome was observed between these subjects and those with a normal APC:SR. Activated protein C sensitivity ratio, modified by pre-dilution of patient samples with factor V depleted plasma, showed no consistent trend with gestation.

Methylergometrine during the early puerperium; a prospective randomized double blind study

Methylergometrine during the early puerperium; a prospective randomized double blind study

Serum concentrations of iodine, thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH) and insulin-like growth factor 1 (IGF-1) during the last trimester of pregnancy, during labour, and in early puerperium of women with normal pregnancy or with in

Summary In women with intrauterine growth retardation (IUGR), insulin-like growth factor 1 (IGF-1) concentrations tended to reduce during the last trimester of pregnancy. Parameters of thyroid function in maternal serum were not distinctly influenced by IUGR, except for high concentrations of iodine. Triiodothyronine (T3) concentrations in cord blood of normal pregnancies was significantly lower than maternal concentrations, but was relatively high when the fetus was growth retarded. The results are discussed in connection with changes of thyroid function and changes of IGF-1 during pregnancy.

Changes in maternal heart dimensions and plasma atrial natriuretic peptide levels in the early puerperium of normal and pre-eclamptic pregnancies.

To measure plasma atrial natriuretic peptide (ANP) in relation to maternal haemodynamics and body fluid balance in the early puerperium following uncomplicated pregnancy and pre-eclampsia. A longitudinal study from late pregnancy and into the early postpartum period (days 1 to 3 and days 4 to 6) compared with nonpregnant controls. Eleven women with uncomplicated pregnancies, 12 women with pre-eclampsia and 12 healthy, nonpregnant women. Maternal heart dimensions determined by M-mode echocardiography, concentrations of ANP, and daily urine output and sodium excretion. After delivery increases in left atrial dimensions, represented as mean (SEM), from 33.2 (1.6) to 37.7 (1.7) mm and ANP levels from 7.9 (1.1) to 19.0 (2.7) pmol/L were observed at 1-3 days postpartum in normal pregnant women, but we were not able to demonstrate a significant increase in diuresis and natriuresis. In the third trimester left atrial dimensions (38.4 (1.2) mm) and ANP levels (15.4 (2.2) pmol/L) were greater in pre-eclampsia. ANP levels rose further in pre-eclamptic women in the early puerperium (27.4 (7.4) pmol/L) with an increase in diuresis and natriuresis, while left atrial dimensions did not change significantly (39.4 (1.7) mm). A pericardial effusion was found in 11 pre-eclamptic but in only three healthy pregnant women. A concommitant increase in left atrial dimensions and ANP in the early puerperium following uncomplicated pregnancies is consistent with the mechanism of atrial stretch as a stimulus for ANP release, although the biological significance of this finding remained unclear. A significantly higher release of ANP in the early puerperium after pregnancies complicated by pre-eclampsia may be a mechanism which promotes the renal elimination of excessive body fluids and sodium.

Ultrasonography of the uterus at early puerperium

Objective: To classify ultrasonic findings of uterus during normal and complicated early puerperium. Methods: One hundred women with normal vaginal delivery and normal puerperium, 29 women with postpartal endometritis and 14 women with excessive postpartal bleeding were examined by ultrasound. Transabdominal ultrasonic examinations were carried out 12–24 h and 4–5 days postpartally. Results: Four main types of ultrasonic findings were associated with normal early puerperium, including echogenic or echolucent areas of less than 2.3 cm anterior-posterior diameter in the uterine cavity. The incidence of a linear central echo representing an empty uterine cavity increased during the first 5 days with simultaneous decrease of the incidence of complex intracavital echoes. No pathognomonic findings associating with puerperal endometritis were diagnosed. A small amount of trophoblastic tissue retention could not be differentiated from the normal postpartal contents of the uterus. Conclusions: The value of ultrasonography for examination of the uterus during early puerperium is limited because of a great physiological variation of the normal findings. Early onset puerperal endometritis and small-sized trophoblastic retention cannot be diagnosed by ultrasound within 1–5 days of vaginal delivery.

Erythrocyte ion and water balance and membrane potential in the puerperium of normal pregnancy.

To examine the balance of erythrocyte ions and water during the rapid changes in plasma osmolality in the early puerperium, and during the subsequent period of sustained readjustment. A serial study from the third trimester of pregnancy to 20 weeks after delivery. Thirty-five primiparous women who had experienced no antenatal complications. Plasma osmolality, erythrocyte hydration, potassium, chloride and sodium were measured and nondiffusible ion content and erythrocyte membrane potential calculated. Plasma sodium, potassium and chloride were also measured. During the first week after delivery plasma osmolality increased (280 (SEM 0.52)-289 (SEM 0.64) mosmol/kg; P < 0.001) but erythrocyte hydration did not decrease (2.060 (SEM 0.018)-2.067 (SEM 0.021) 1/kg dry cells) because of an increase in total cell osmole content (577 (SEM 5.31)-597 (SEM 6.15) mosmol/kg dry cells; P = 0.001). This increase included nondiffusible anions, chloride and potassium. These changes in ionic balance did not affect membrane potential. After the first week of the puerperium and up to the 20th week, plasma osmolality was stable but erythrocyte osmole content and hydration both decreased. This was due to a decrease in nondiffusible anions and potassium with a smaller increase in chloride leading to a decrease in membrane potential (-14.31 (SEM 0.34)mV to -12.66 (SEM 0.28)mV; P < 0.001). A rapid increase in intracellular osmoles can occur in the mature erythrocyte and probably precedes the decrease in plasma osmolality in the puerperium. Changes in erythrocyte homeostasis in the first week of the puerperium can be accounted for by alterations in nondiffusible anions. After the first week of the puerperium it appears that the functional organisation of the membrane is changing.

Blues and depression during early puerperium: Home versus hospital deliveries

Blues and depression during early puerperium: Home versus hospital deliveries

Urinary phenylethylamine and cortisol levels in the early puerperium

Phenylethylamine and cortisol were measured in 24-h urine samples taken from women day 2 3 postpartum, and matched controls. They also completed self-rating blues and highs scales. There was no significant difference in phenylethylamine excretion in those who scored highly with blues or highs, and either postpartum or normal controls. The number of raised values for phenylethylamine output was significantly greater in the postpartum women, who had no psychopathology, than in normal controls. Cortisol levels were significantly raised in postpartum controls compared with normal controls; women with the highs excreted significantly less cortisol than other postpartum women.

Elevation of serum creatine phosphokinase and its MB isoenzyme during normal labor and early puerperium

Chest pain or discomfort are infrequent complaints among women during labor and early puerperium, but when present they raise the suspicion of myocardial ischemia. The diagnosis of the latter is based upon serum elevatIon of certain enzymes, such as aspartate amino transferase, lactate dehydrogenase and creatine phosphokinase. Nevertheless, the normal patterns of these enzymes in the serum during labor and early puerperium have not been characterized well. To determine serum creatine phosphokinase, lactate dehydrogenase and aspartate amino transferase levels in late pregnancy, and throughout labor and early puerperium. Fifty women having normal pregnancies followed by uneventful vaginal deliveries were prospectively studied for serum lactate dehydrogenase, aspartate amino transferase and creatine phosphokinase including its MB isoenzyme before, during and after labor. Cardiac status was evaluated in all women using serial electrocardiographic and physical examinations. All women were found to have low to normal antepartum serum enzymes levels. However, during labor total creatine phosphokinase increased markedly, reaching a peak of 2-4 fold baseline levels 24 hours postpartum. It then declined gradually back to baseline. Nulliparous women reached substantially higher levels than multiparous women. The MB or so-called cardio-specific isoenzyme was found to be an important contributor to creatine phosphokinase surge in most women. Correlation was demonstrated between length of the active phase of labor and both total and MB creatine phosphokinase activity. There was no clinical or electrocardiographic evidence for cardiac muscle damage in any of the study patients. Serum lactate dehydrogenase and aspartate amino transferase were not altered during or after labor. Serum total creatine phosphokinase and its MB isoenzyme increase substantially during normal vaginal labor without evidence of myocardial ischemia. The uterus and placenta, two organs which were reported to embody substantial amounts of these enzymes, and which participate actively in the process of labor, are thought to release these enzymes to the circulation during labor. Knowing the normal patterns of these enzymes in the serum during labor and puerperium may prevent erroneous diagnoses of myocardial ischemia or infarction. Lack of electrocardiographic abnormalities and low lactate dehydrogenase and aspartate amino transferase levels may assist in excluding such diagnoses.

Lymphocyte subsets and mitogen stimulation of blood lymphocytes in normal pregnancy.

In normal pregnancy the maternal immune system should be directed towards tolerance or suppression in order not to reject the partly foreign feto-placental unit. The aim of this investigation was to find hallmarks of systemic immunosuppression during normal pregnancy. Five healthy primigravidae were examined during pregnancy and postpartum with flow cytometric analysis to define T and B lymphocyte subsets in peripheral blood. In addition, we studied the proliferative response of lymphocytes to mitogens or interleukin-2 (IL-2) alone or in combination with immunomodulating drugs or interleukin-4 (IL-4). The results were compared to healthy, non-pregnant women. During pregnancy and early puerperium we noted an immune balance in favour of suppression, as measured by increased numbers of T "helper/suppressor" (CD4+CD45RA+) and "suppressor"/effector T cells (CD8+S6F1-), and decreased numbers of T "helper/inducer" (CD4+CD29+), T "helper/memory" (CD4+CD45RO+), killer/effector T cells (CD8+S6F1+), and Natural Killer cells (CD56+), as well as decreased numbers of activated lymphocytes expressing IL-2 receptor (CD25+) and T cells expressing HLA-DR (HLA-DR+CD3+). During pregnancy, lymphocyte proliferation was impaired in autologous serum with concanavalin A (ConA), phytohemagglutinin (PHA), or IL-2. A difference in proliferative response to PHA or IL-2 between cultures with AB serum and autologous serum is suggestive of an immunosuppressor factor in serum during pregnancy. Indomethacin significantly increased lymphocyte proliferation in autologous serum with ConA, indicating PGE2 mediated suppressor activity during pregnancy. Chlorambucil and cimetidine modulated the proliferative response to ConA, indicating an alkylating agent sensitive and a histamine dependent suppressor activity during pregnancy. During normal pregnancy, a state of systemic suppression of the maternal immune system seems to be present.

Peripartum cardiomyopathy

Congestive heart failure is an uncommon complication of pregnancy with potentially life-threatening consequences. Peripartum cardiomyopathy is a disease of unknown cause in which severe left ventricular dysfunction occurs during late pregnancy or the early puerperium. In the past, the diagnosis of this entity was made on clinical grounds; however, modern echocardiographic techniques have allowed more accurate diagnoses by excluding cases of diseases that mimic the clinical symptoms and signs of heart failure. Risk factors for peripartum cardiomyopathy include advanced maternal age, multiparity, African descent, twinning, and long-term tocolysis. An extensive search for the causes of peripartum cardiomyopathy has been unrevealing. Treatment includes digitalis, diuretic agents, and vasodilators. Anticoagulation is strongly recommended, especially if ventricular function is persistent. The prognosis of peripartum cardiomyopathy is related to the recovery of ventricular function. Caution is advised in recommending subsequent pregnancy, especially if left ventricular dysfunction is persistent.

Blues and depression during early puerperium: home versus hospital deliveries.

To investigate whether women who give birth at home are less prone to mood disturbances during the early puerperium than those who give birth in hospital. A prospective study of 303 pregnant women who registered for antenatal care. The antenatal clinic at St Joseph's Hospital, Veldhoven, The Netherlands, and five antenatal consultation programmes of local midwives working in the surrounding region. Three hundred and eighty-two consecutive caucasian women registering for antenatal care were approached. Of these, 303 consented to participate and 293 completed the study. The predictor variable was the way in which the women gave birth: spontaneous vaginal parturition at home or in hospital as follows: spontaneously; vaginal parturition after stimulation with medication; vaginal parturition with forceps/vacuum extraction; or caesarean section. The outcome variables were blues and depression. The occurrence of blues was assessed at 4 weeks postpartum, using Pitt's criteria. The occurrence of depression was assessed at 4 weeks postpartum using the Research Diagnostic Criteria. The possible confounding effects of a set of obstetrical and psycho-social variables relating to the early puerperium were investigated using logistic regression analysis. Of the 293 women who completed the study, 52% gave birth at home. Significantly more nullipara gave birth in hospital. Parturition occurred where it had been planned in 77% of women; referral occurred later on in pregnancy in 11% and during labour in 12%. Nullipara had to be referred significantly more often than multipara. In general, there was no difference in the incidence of blues and depression between women who gave birth at home and those who gave birth in hospital. Obstetric factors were not related to the occurrence of blues or depression in the early puerperium. Women who gave birth in hospital are no more prone to postpartum mood disturbances, such as blues and depression, than women who give birth at home.