Augmentation index and pulse wave velocity in normotensive and pre-eclamptic pregnancies.

OBJECTIVE: Hypertensive disorders during pregnancy remain a major health burden. Normal pregnancy is associated with systemic cardiovascular adaptation. The augmentation index and pulse wave velocity measures may serve as surrogate markers of cardiovascular pathology, including pre-eclampsia. We evaluated these parameters during and after normotensive and pre-eclamptic pregnancies. DESIGN: Longitudinal cohort trial involving a case-control analysis of healthy women and women with pre-eclampsia. SETTING: University hospital. POPULATION: Fifty-three healthy pregnant women between 11(+6) and 13(+6) gestational weeks, as well as 21 patients with pre-eclampsia. METHODS: The augmentation index and pulse wave velocity were measured seven times during pregnancy and postpartum. MAIN OUTCOME MEASURES: Changes in augmentation index and pulse wave velocity during and after healthy pregnancies were measured. The influence of early-onset and late-onset pre-eclampsia on these measurements both during and after pregnancy was evaluated. RESULTS: The normotensive pregnancies exhibited a significant decrease in the augmentation index from the first trimester to the end of the second trimester; however, the normotensive pregnancies showed an increase in the augmentation index during the third trimester as term approached. The patients with early-onset and late-onset pre-eclampsia displayed a significantly elevated augmentation index during pregnancy. The postpartum augmentation index and pulse wave velocity were significantly elevated in the early-onset pre-eclampsia group. CONCLUSION: After pregnancy, early-onset and late-onset pre-eclamptic patients exhibit differences in vascular function. This result indicates the presence of a higher cardiovascular risk in patients after early-onset pre-eclampsia.

Diagnostic biomarkers of pro-inflammatory immune-mediated preterm birth.

PURPOSE: Pro-inflammatory immunity, either infectious or sterile-derived, is one of the major causes of preterm birth and associated with enhanced maternal and fetal morbidity and mortality. Diagnosing intrauterine inflammation at an early stage is tremendously important. Amniotic fluid interleukin (IL)-6 concentration is currently the most investigated diagnostic tool for detecting intrauterine inflammation. METHODS: Amniotic fluid samples were obtained from women with no signs of intrauterine infection [amniocentesis (n = 82), cesarean section (n = 110), spontaneous delivery (n = 20) and those with clinical signs of intrauterine infection or inflammation (AIS, n = 16)]. Amniotic fluid was screened by commercial ELISAs for IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, growth regulated oncogene-α (gro) α, macrophage inflammatory protein (MIP) 1α, MIP1ß, histone, tumor necrosis factor (TNF) α, proIL1ß and interferon γ-induced protein (IP) 10. RESULTS: ProIL-1ß, MIP1ß, IL-10 and IL-8 levels were significantly elevated in the AIS group, whereas IL-4 levels were significantly lower in the AIS group. No significant differences were found regarding IL-2, IL-6, IL-12, IL-15, IL-17, GROα, MIP1α, histone, TNFα, ProIL1ß and IP10. CONCLUSION: MIP1ß, IL-4, IL-8, IL-10 and proIL-1ß might be potential singular biomarkers in diagnosing intrauterine inflammation. The combinations of elevated levels of IL-17/GROα, MIP1ß/IL-15 and histone/IL-10 are new potentially advantageous biomarker combinations.

Maternal and fetal cord blood lipids in intrauterine growth restriction.

AIM: Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses. METHODS: Umbilical cord serum lipids and oxidative modified, low-density lipoprotein (oxLDL) concentrations were measured by colorimetric enzymatic measurements, or by ELISA. Values of IUGR (n=36) and constitutionally small for gestational age neonates (SGA, n=22) were compared with those of healthy, adequate for gestational age, born neonates (CN, n=97). SAS-statistic software was used and two-way ANOVA was adjusted for gestational age at delivery. RESULTS: Fetal high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) concentrations were found to be lower in the IUGR compared to the CN and SGA groups (HDL-C: P<0.001, TC: P<0.01). Atherogenic indices, including the oxLDL/LDL-C ratio, were increased in the IUGR compared to the CN group (oxLDL/LDL-C ratio: P<0.001). CONCLUSION: Our results support the hypothesis of a disturbed cholesterol supply in IUGR fetuses. Born SGA has been shown to be a risk factor for developing cardiovascular disease later in life. Since HDL-C has anti-inflammatory properties, a reduced HDL-C during fetal development, and an increase in atherogenic indices, might provide a link to this observation in IUGR fetuses.

Inhibin/activin-betaE subunit is expressed in normal and pathological human placental tissue including chorionic carcinoma cell lines.

BACKGROUND: Inhibins and activins are important regulators of the female reproductive system. Recently, a novel inhibin subunit, named betaE, has been identified and shown to be expressed in several human tissues. However, only limited data on the expression of this novel inhibin-betaE subunit in normal and pathological human placenta as well as and human chorionic carcinoma cell lines exist. MATERIALS AND METHODS: Tissue specimens of normal, preeclamptic and HELLP pregnancies (n = 18) were obtained at the course of an cesarean section. Normal and pathological placental tissues as well as chorionic carcinoma cells (BeWo and JEG) were analyzed by using immunohistochemistry and RT-PCR. RESULTS: Expression of the inhibin betaE subunit could be demonstrated at the protein level by means of immunohistochemical evaluation and at the transcriptional level by betaE-specific RT-PCR analysis. The immunoreactive score for inhibin-betaE did not show any significant differences between normal, preeclamptic and HELLP tissue in extravillous trophoblast and syncytiotrophoblast cells. Expression of inhibin betaE could further be demonstrated for the human chorionic carcinoma cell lines JEG and BeWo. DISCUSSION: We demonstrated that inhibin-betaE is expressed in normal and pathological human placenta tissues. Although the precise role of this novel inhibin subunit for human placenta development is quite unclear, similarities with the well-characterized betaA- and betaB-subunits suggest an involvement in autocrine/paracrine signaling pathways, angiogenesis, decidualization and tissue remodeling under normal as well as malignant conditions. Additionally, the human chorionic carcinoma cell lines JEG and BeWo synthesize this subunit and therefore can be used as a cell culture model for further functional analysis of this subunit in human placental tissue.

NT-proBNP is increased in healthy pregnancies compared to non-pregnant controls.

Serum concentrations of the amino-terminal pro-B-type natriuretic peptide (NT-proBNP) may be used to monitor cardiac function during pregnancy but normal values are not established for this purpose. Therefore, we investigated NT-proBNP in normotensive healthy pregnancies compared to a non-pregnant control group. Serum NT-proBNP was measured in 94 normotensive, healthy pregnant women (32+/-6 years) every five weeks beginning from 12th gestational week (GW) in a longitudinal study and compared to a non-pregnant control group of 521 women (32+/-7 years). Pooled median serum NT-proBNP levels (25th; 75th percentile) were significantly higher in pregnant women compared to non-pregnant women (56 (33; 95) pg/ml vs. 38 (22; 62) pg/ml (p<0.001)). NT-proBNP increased during pregnancy to 73 (51; 124) pg/ml in the 11+6 to 15+6 GW (p<0.001). However, NT-proBNP levels from 23+0 GW towards term were comparable to non-pregnant controls. NT-proBNP is significantly elevated in healthy pregnancies until mid-pregnancy. As preeclampsia and gestational hypertension are associated with increased NT-proBNP, our results have to be considered in future diagnostic approaches using NT-proBNP for these pathologic conditions.

Stillbirth following previous cesarean section in Bavaria/Germany 1987-2005.

BACKGROUND: An elevated risk for unexplained stillbirth in subsequent pregnancies after cesarean section was reported in 2003. This finding would imply renewed discussions about stronger indications for cesarean sections. OBJECTIVE: To find out whether there is an elevated risk for stillbirth in subsequent pregnancies after cesarean section in our cohort in Bavaria. METHODS: As data linkage of records is not possible in Germany, we devised a suitable adjustment for bias correction. Second pregnancies in Bavaria/Germany after previous vaginal birth and previous cesarean section from 1987 to 2005 were analyzed. Risk of unexplained stillbirth was estimated by time-to-event analysis. RESULTS: In our cohort of 629,815 second pregnancies, no elevated stillbirth risk in pregnancies after previous cesarean section compared to previous vaginal birth was noted (crude risk 0.22% in both groups; hazard ratio (HR) 1.00; P = 1.0). A slightly decreased risk for stillbirth after previous cesarean section for the period of 1994-2005 (HR 0.674; P = 0.04) could be shown. CONCLUSION: We found no elevated stillbirth risk in pregnancies after previous cesarean section. The significantly lower risk for stillbirths after previous cesarean section in the period 1994-2005 is interpreted as consequence of improved obstetric surveillance. With our adjustment for bias correction, we hope to have found a way to make our data largely comparable with other sources reported in the literature. However, because of the strict German data protection act, the Bavarian birth register is only of limited use for the presented study.

Inflammatory response in preeclampsia.

The origin of preeclampsia, a disease unique to pregnancy is still matter of debate and numerous theories have been proposed. The pathophysiology of the disease involves impaired trophoblast invasion, abnormal genetic polymorphism, vascular endothelial cell activation, immune intolerance by the maternal immune system, but also an exaggeration of a systemic inflammatory process. Preeclampsia is one of the major causes of maternal and perinatal morbidities including preterm births and therefore merits ongoing intensive research. The inflammatory process is determined by immunogenetic and non-immunogenetic factors. While inflammation mostly appears to be related to immunogenic determinants such as HLA antigens, paternity, monocytes, proinflammatory cytokines and NK cells, also responses not directly related to the immune system have been observed such as related to hypoxia or agonistic autoantibodies directed against vasoconstrictive angiotensin II receptors. The HIF-modulated reactions open up a new field in research as recently published data show the complexity of these factors.

Expression of E-cadherin and its repressor snail in placental tissue of normal, preeclamptic and HELLP pregnancies.

Incomplete invasion of extravillous trophoblasts (EVT) is thought to be associated with complications of pregnancy. Snail, a zinc-finger transcription factor represses the transcription of the cell adhesion molecule E-cadherin. The aim of this study was to investigate the expression of E-cadherin and Snail in placental tissue with preeclampsia or HELLP. Placental tissues were obtained from five patients with HELLP syndrome, seven patients with preeclampsia and seven patients after a normal term birth and analysed for Snail and E-cadherin immunoreactivity with specific monoclonal antibodies. Immunohistochemical staining of the placental tissue was analysed using an immunoreactivity score for the evaluation of staining intensity. In preeclamptic EVT, Snail immunoreactivity showed a significant 1.7-fold increase, accompanied by a significant 1.9-fold reduction of E-cadherin immunoreactivity. A 1.7-fold increase of Snail and in parallel a 1.3-fold reduction of E-cadherin was observed in EVT of HELLP placentas although without statistical significance. Loss of E-cadherin can be observed during epithelial-mesenchymal transition (EMT), a key process in normal development and trophoblast differentiation. Snail represses the transcription of E-cadherin triggering a complete EMT. Results obtained in this study showed changes of Snail and E-cadherin immunoreactivity in preeclamptic placentas that could be accompanied with an altered EMT in trophoblasts.

Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy.

Remodeling of uterine spiral arteries is critical for the continuation of a successful pregnancy. Uterine natural killer (uNK) cells are the predominant leukocyte population in the early pregnant decidua, and a role for these cells in spiral artery remodeling in pregnancy has been suggested. Angiogenic growth factors were measured in isolated uNK and total (unseparated) decidual cells (8-10 or 12-14 weeks gestation, n=5 each gestational age) after culture for 48 h. Angiopoietin (Ang)1, placental growth factor, transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor (VEGF)-C were measured by enzyme-linked immunosorbent assay. Angiogenin, Ang2, fibroblast growth factor basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth factor (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a FASTQuant angiogenic growth factor multiplex protein assay. Levels of Ang2, ICAM-1, and KGF, secreted by the total decidual fraction, decreased with increasing gestational age. uNK levels of Ang2 and VEGF-C also decreased with increasing gestational age. At 8-10 weeks gestation, there was no difference in the level of Ang1, Ang2, TGF-beta1, and VEGF-C secreted by uNK cells and the total decidual fraction. At 12-14 weeks, uNK cells secreted significantly lower levels of VEGF-C than the total decidual fraction. Early pregnancy decidua is a major source of angiogenic growth factors whose levels decrease with increasing gestational age, suggesting that they may play a role in spiral artery remodeling. uNK cells appear to be a prominent source of Ang1, Ang2, TGF-beta1, and VEGF-C within the placental bed.

Role of placental growth hormone in the alteration of maternal arterial resistance in pregnancy.

OBJECTIVE: To investigate the relation between arterial resistance and placental growth hormone (hGH-V) levels in the maternal circulation. STUDY DESIGN: Sixty-seven women with normal pregnancy, 13 with preeclampsia (PE) and 11 with intrauterine fetal growth restriction (IUGR) underwent Doppler sonography of the placental and nonplacental uterine and cubital artery and blood sampling. hGH-V was measured with a highly sensitive sandwich-type immunofluorometric assay and pituitary growth hormone (hGH-N) and insulinlike growth factor I (IGF-I) with a chemiluminescence assay. A p value of < 0.05 was considered significant. RESULTS: During normal pregnancy the arterial pulsatility index (PI) decreased (p < 0.001), serum levels of hGH-V and IGF-I increased (p < 0.0001), and hGH-N decreased (p < 0.0001). Pathologic pregnancies (PE, IUGR) showed a significant higher PI in all arteries, but hGH-V and the IGF-I were decreased. CONCLUSION: Our data demonstrate a strong correlation between decreasing uterine and peripheral arterial resistance and increasing hGH-V during normal pregnancies with impaired uterine blood flow there were lowered serum levels of hGH-V, hGH-N and IGF-I. Lower levels of hGH-V and hGH-N might contribute to impaired uteroplacental circulation.

Expression of estrogen receptor-alpha, estrogen receptor-beta and placental endothelial and inducible NO synthase in intrauterine growth-restricted and normal placentals.

BACKGROUND: Nitric oxide seems to play important roles in the physiology of placental blood circulation, although their expression in pathological placentas and their role is still unclear. Therefore, the aim of this study was to investigate the expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta) and the endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) in intrauterine growth-restricted (IUGR) placentas, hemolysis, elevated liver enzymes, low platelets (HELLP) placentas and in normal healthy control placentas. METHODS: Slides of paraffin-embedded placental tissue were obtained after delivery from patients diagnosed with IUGR, HELLP and normal term placentas and analyzed for eNOS and iNOS, as well as ERalpha/beta expression. Intensity of immunohistochemical reaction was analyzed using a semi-quantitative score, and statistical analysis was performed. In addition, Western blot experiments were performed for comparison of staining intensities obtained by immunohistochemistry and Western blot. RESULTS: Expression of eNOS and iNOS is significantly reduced in trophoblast cells of placentas with HELLP. However, ERbeta expression in HELLP placentas demonstrated a significantly elevated expression intensity compared to normal controls. ERalpha expression was not significantly different in all three pathologies investigated. CONCLUSIONS: We speculate that the increased ERbeta expression in both syncytiotrophoblast and extravillous trophoblast cells represents accelerated proliferation of placental tissue or can be seen as a compensatory effect in HELLP placentas.

Expression of endothelial NO synthase, inducible NO synthase, and estrogen receptors alpha and beta in placental tissue of normal, preeclamptic, and intrauterine growth-restricted pregnancies.

In the physiology of placental blood circulation, nitric oxide (NO) synthases seem to play important roles, although their expression in pathological placentas and their role is still unclear. In addition, NO synthase activation seems to be related to estrogen receptor expression. Therefore, the aims of this study were to investigate the expression of estrogen receptors alpha (ERalpha), estrogen receptor beta (ER and the endothelial NO synthase (eNOS), and inducible NO synthase (iNOS) in intrauterine growth-restricted (IUGR) placentas, preeclamptic placentas, and in normal healthy control placentas. Slides of paraffin-embedded placental tissue were obtained after delivery from patients diagnosed with IUGR, preeclampsia, and normal term placentas and analyzed for eNOS, iNOS as well as ERalpha and ERbeta expression. Intensity of immunohistochemical reaction was analyzed using a semiquantitative score and statistical analysis was performed. In addition, Western blot experiments were performed for comparison of staining intensities obtained by immunohistochemistry and western blot. Expression of eNOS, iNOS, and ERbeta is significantly reduced in trophoblast cells of placentas with IUGR. However, preeclamptic placentas demonstrated a significant elevated expression intensity of these proteins compared with normal controls. A different expression of eNOS, iNOS, ERalpha, and ERbeta by human trophoblast cells seems to results in lower NO output and impaired trophoblast invasion. Results obtained in our study provide evidence that reduced expression of the investigated proteins is related to IUGR.

A new nonisotopic, highly sensitive assay for the measurement of human placental growth hormone: development and clinical implications.

Human placental GH (hGH-V) is a variant of pituitary hGH (hGH-N) synthesized and secreted by syncytiotrophoblasts during pregnancy. It differs from hGH-V by only 13 amino acid residues, which makes difficult a specific measurement of hGH-V without interference from hGH-N. To overcome the analytical difficulties, we produced new high affinity monoclonal antibodies specific for hGH-V. Precise screening and epitope mapping allowed identification of a pair of monoclonal antibodies suitable to establish a highly sensitive assay for hGH-V measurement. In a prospective, longitudinal study involving 84 normal pregnancies, we measured maternal concentrations of hGH-V, leptin, IGF-I, and cord blood IGF-I. hGH-V was detectable as early as gestational week (GW) 7. Mean concentrations of hGH-V increased from 0.9 +/- 0.5 microg/liter (GW 7-13) to 2.8 +/- 0.9 microg/liter (GW 18-22), 7.3 +/- 2.6 microg/liter (GW 28-32), and 13.0 +/- 9.6 (GW 37-41). A negative correlation was found between prepregnancy body mass index and hGH-V concentrations from GW 28 onward. Peak hGH-V levels occurred at wk 36.5 +/- 2.6 and were significantly lower in obese (P = 0.029) and higher in underweight (P = 0.035) mothers compared with those in mothers of normal weight. The increase in hGH-V between GW 18-22 and GW 28-32 was negatively correlated to the increase in maternal leptin during this period (P = 0.027). Maternal IGF-I concentrations were correlated to those of hGH-V from GW 18 onward (P = 0.039). The strongest correlation was found at GW 28-32 (P = 0.001). Furthermore, maternal hGH-V concentrations in late pregnancy correlated with cord blood IGF-I (P = 0.025) and size of the newborn (P = 0.017). These results, obtained by a new, highly sensitive hGH-V-specific immunoassay, highlight the importance of maternal hGH-V in the regulation of maternal and fetal IGF-I. In addition, the results indicate that maternal weight has a major impact on circulating concentrations of hGH-V.

The evaluation of the oxidative state of low-density lipoproteins in intrauterine growth restriction and preeclampsia.

OBJECTIVE: To evaluate the oxidative state of lipoproteins in pregnancies complicated by intrauterine growth restriction (IUGR) in comparison to preeclampsia (PE) and healthy pregnant control subjects (CN). METHODS: Maternal serum of 20 PE, 29 IUGR, and 29 gestational age-matched CN were analyzed. Total cholesterol (TC), low-density lipoprotein (LDL)-bound cholesterol (LDL-C), and oxidized LDL (oxLDL) concentration were measured once between 25 and 34 weeks of gestation. Statistical estimates were performed by Student's t-test. RESULTS: Serum concentrations of LDL-C and TC were significantly reduced in IUGR [LDL-C: CN - mean = 146 mg/dL, SD = ± 40.1; IUGR - mean = 102 mg/dL, SD = ± 27.3 (p < 0.0001); PE - mean = 130 mg/dL, SD = 38.8 mg/dL; TC: CN - mean = 259/dL, SD = ± 46.8; IUGR - mean = 218 mg/dL, SD = ± 35.0 (p < 0.001); PE - mean = 244 mg/dL, SD = 48.2]. There was no significant difference in oxLDL/LDL-C ratio within the three groups (CN: mean = 0.76, SD = 0.24; IUGR: mean = 0.74, SD = 0.12; PE: mean = 0.77, SD = 0.22). CONCLUSION: Our results show a lower maternal LDL-C and TC concentration in IUGR pregnancies. These data contribute to the hypothesis of a decreased cholesterol supply to the fetus in IUGR. However, we could not confirm the hypothesis of an altered oxidative state in neither IUGR nor PE.

Influence of maternal age, gestational age and fetal gender on expression of immune mediators in amniotic fluid.

BACKGROUND: Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated. FINDINGS: Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GRO-alpha, MIP1alpha, MIP1beta, Histone, and IP10. Analysis was by Bonferroni correction for multiple comparisons. None of the 15 examined cytokines revealed any differences in expression patterns regarding fetal gender. Significant differences were found in IL-4, IL-10, IL-12, TNF- alpha, GRO-alpha and MIP1-beta with respect to gestational age and in GRO-alpha regarding maternal age. CONCLUSION: Cytokines utilized as biomarkers in the diagnosis of intrauterine infections are not influenced in their expression pattern by fetal gender but may vary with respect to maternal age and gestational age.

Inhibin-betaC subunit expression in normal and pathological human placental tissues.

Inhibins and activins are important regulators of the female reproductive system. Recently, a novel inhibin betaC subunit has been identified. However, only limited data on the expression of this novel inhibin-betaC subunit in normal and pathological human placentas exist. Tissue specimens of normal, preeclamptic, hemolysis, elevated liver enzymes, low platelets (HELLP), and intrauterine growth restriction (IUGR) pregnancies (n=24) were obtained at the conclusion of a cesarean section. Normal and pathological placental tissues were analyzed by an immunohistochemical staining reaction with a specific antibody against this novel inhibin-betaC subunit. Overall, expression of the inhibin-betaC subunit could be demonstrated in normal and pathological placental tissue. The immunoreactive score (IRS) for inhibin-betaC did not show any significant differences between normal, preeclamptic, HELLP, and IUGR tissue in extravillous trophoblast and syncytiotrophoblast cells. Immunolabelling of this novel inhibin-ßC protein in normal and pathological placental tissue was demonstrated, although no differences in the staining intensity could be observed. Therefore, the inhibin-ßC isoform might not primarily be involved in the pathogenesis of these pregnancy-associated disorders. The functional role of this novel inhibin-betaC subunit in normal and pathological human placenta is still quite unclear and should thus be further investigated.

[Pregnancy screening in Germany]. / Schwangerenvorsorge in Deutschland.

Antenatal care in Germany is regulated by so-called national maternity health guidelines. The aim is to detect pregnancies at risk and potential high-risk deliveries in order to initiate risk-adapted treatment. The guidelines include 3 sonographic examinations as well as serological and infectious diagnostics. So far the glucose tolerance test is not integrated and needs individual indication.

Temporal trends in pregnancy weight gain and birth weight in Bavaria 2000-2007: slightly decreasing birth weight with increasing weight gain in pregnancy.

AIMS: To assess temporal trends in birth weight and pregnancy weight gain in Bavaria from 2000 to 2007. METHODS: Data on 695,707 mother and infant pairs (singleton term births) were available from a compulsory reporting system for quality assurance, including information on birth weight, maternal weight at delivery and at booking, maternal smoking, age, and further anthropometric and lifestyle factors. Pregnancy weight gain was defined as: weight prior to delivery minus weight at first booking minus weight of the newborn. RESULTS: Although mean weight gain during pregnancy increased considerably from 10.10 to 10.73 kg in seven years, the mean birth weight in mature singletons decreased slightly from 3433 to 3414 g. These trends could not be explained by concurrent changes in the rates of primiparity, smoking and gestational diabetes. CONCLUSIONS: These German data confirm an increased weight gain during pregnancy with adjustment for potential confounders.

Optimal gestational weight gain ranges for the avoidance of adverse birth weight outcomes: a novel approach.

BACKGROUND: Gestational weight gain (GWG) has been shown to be directly associated with birth weight. OBJECTIVE: We aimed to define ranges for optimal GWG with respect to the risk of either small- or large-for-gestational-age offspring by using a new statistical approach. DESIGN: For the purpose of an observational study, data on n = 177,079 mature singleton deliveries in Bavaria between 2004 and 2006 were extracted from a standard data set that is regularly collected for national benchmarking of obstetric units in terms of clinical performance. Joint predicted risks of either small- or large-for-gestational-age births in relation to GWG (continuous measurement) were estimated by logistic regression models with adjustment for potential confounders. RESULTS: The estimated optimal GWG ranges as defined by a joint predicted risk of