Decreased maternal circulating hepatocyte growth factor (HGF) concentrations in pregnancies with small for gestational age infants

Our purpose was to evaluate whether maternal and fetal hepatocytegrowth factor (HGF) concentrations in pregnancies with smallfor gestational age (SGA) infants are different from those inpregnancies with appropriate for gestational age (AGA) infants.Maternal and fetal circulating HGF concentrations were comparedbetween 55 pregnancies with AGA infants and 16 pregnancies withSGA infants at birth. HGF concentrations were measured frommaternal and cord venous blood samples using an enzyme-linkedimmunosorbent assay. Umbilical artery blood pH and oxidativepressure (PO₂) were also measured. Maternal circulating HGFconcentrations (0.60 ± 0.35 ng/ml) in pregnancies withSGA infants were significantly lower than those (0.91 ±0.44 ng/ml) in pregnancies with AGA infants (P = 0.012). Therewere no significant differences in fetal circulating HGF concentrationsbetween both groups. No significant differences in umbilicalartery blood pH and PO₂ were found between both groups. Theseresults suggest that the maternal serum circulating HGF concentrationhas a significant role in fetal growth during pregnancy.     

Maternal and fetal nitric oxide synthesis is decreased in pregnancies with small for gestational age infants

Our purpose was to evaluate whether maternal and fetal nitric oxide synthesis in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. Maternal and fetal circulating nitrate and nitrite concentrations were compared between 30 pregnancies with AGA and 10 pregnancies with SGA at birth. End-products of nitric oxide synthesis were measured in maternal and cord venous blood samples using a fluorometric assay. Umbilical artery blood pH and PO2 were also measured. Maternal circulating nitrite and nitrate concentrations (6.91 +/- 1.27 microM) in pregnancies with SGA were significantly lower than those (11.69 +/- 1.33 microM) in pregnancies with AGA (P = 0.015). Fetal circulating nitrite and nitrate concentrations (7.54 +/- 1.09 microM) in pregnancies with SGA were also significantly lower than those (11.24 +/- 1.08 microM) in pregnancies with AGA (P = 0.024). There were no significant differences in umbilical artery blood pH and PO2 between the two groups. These results suggest that maternal and fetal nitric oxide synthesis are decreased in pregnancies with SGA infants.      

Human placental growth hormone is increased in maternal serum at 20 weeks of gestation in pregnancies with large-for-gestational-age babies

To investigate the relationship between maternal serum concentrations of placental growth hormone (GH-V), insulin-like growth factor (IGF)-1 and 2, IGF binding proteins (IGFBP)-1 and 3 and birth weight in appropriate-for-gestational-age (AGA), large-for-gestational-age (LGA) and small-for-gestational-age (SGA) cases in a nested case-control study. Maternal serum samples were selected from the Screening for Pregnancy Endpoints (SCOPE) biobank in Auckland, New Zealand. Serum hormone concentrations were determined by ELISA. We found that maternal serum GH-V concentrations at 20 weeks of gestation in LGA pregnancies were significantly higher than in AGA and SGA pregnancies. Maternal GH-V concentrations were positively correlated to birth weights and customized birth weight centiles, while IGFBP-1 concentrations were inversely related to birth weights and customized birth weight centiles. Our findings suggest that maternal serum GH-V and IGFBP-1 concentrations at 20 weeks' gestation are associated with fetal growth.     

Elevation of amniotic fluid macrophage colony-stimulating factor in normotensive pregnancies that delivered small-for-gestational-age infants

PROBLEM: Macrophage colony-stimulating factor (M-CSF) promotes placental growth and maintenance. We evaluated whether amniotic fluid M-CSF levels were altered in normotensive pregnancies that produced small-for-gestational-age (SGA) infants arising from unknown factors. METHOD OF STUDY: This study enrolled 68 Japanese women experiencing normotensive pregnancies with single fetuses. Of these pregnancies, 22 delivered SGA infants arising from unknown factors (SGA group); one delivered an SGA infant with intestinal obstruction. The other 45 were women who delivered appropriate-for-gestational-age (AGA) infants (AGA group). They were selected as controls. Amniotic fluid was collected and the M-CSF levels were compared between the two groups. The M-CSF level was determined by enzyme-linked immunosorbent assay method. RESULTS: Amniotic fluid M-CSF concentrations were 6525 pg/mL (median) in the SGA group and 4790 pg/mL in the AGA group; the concentrations were significantly higher in the SGA group than in the AGA group. The M-CSF concentrations in the woman who delivered an SGA infant with intestinal obstruction showed very high values (24290 pg/mL). CONCLUSION: We demonstrated a significant increase in amniotic fluid M-CSF levels in the SGA group. Excessive concentrations of M-CSF in amniotic fluid via amniotic membranes may be highly related to immunological abnormalities contributing to low birth weight of neonates.     

Birth weight in offspring of mothers with polycystic ovarian syndrome

BACKGROUND: A relationship between reduced fetal growth and the polycystic ovary syndrome (PCOS) has been proposed in girls with PCOS. However, the birth weight in the offspring of PCOS mothers has not been systematically investigated. The aim of this study was to establish the birth weight of newborns of mothers with PCOS and to compare it with a control group of newborns of normal women matched by age and weight at the beginning of pregnancy. METHODS: The birth weight of 47 infants born from singleton pregnancies in women with well-documented PCOS was compared with 180 infants born from singleton pregnancies in healthy controls. RESULTS: The prevalence of small for gestational age (SGA) infants was significantly higher in the PCOS group compared to the control group (12. 8% versus 2.8%, respectively, P<0.02). Moreover, SGA infants born to PCOS mothers were smaller than those born to control mothers (P<0.05). The prevalence of large for gestational age infants (LGA) was similar in both groups, but birth length of LGA newborns was greater in PCOS women than controls (P<0.05). CONCLUSIONS: PCOS mothers showed a significantly higher prevalence of SGA newborns which cannot be completely attributed to pregnancy complications, and seems to be more related to the PCOS condition of the mother.     

血管内皮生长因子及其可溶性血管内皮生长因子受体-1水平与胎儿出生体重

目的本研究通过对比血管内皮生长因子(VEGF)、可溶性血管内皮生长因子受体-1(sFlt-1)水平差异与新生儿出生体重的关系,以探讨其在胎儿出生体重发生中的作用。方法采用免疫组织化学法检测40例分娩正常出生体重儿组(AGA组)、30例高出生体重儿组(LGA组)及30例低出生体重儿组(SGA组)胎盘组织中VEGF、sFlt-1的表达水平。结果①LGA组胎盘组织中VEGF的表达高于AGA组,sFlt-1的表达水平低于AGA组,差异有统计学意义(χ2=21.17,P<0.01)。SGA组胎盘组织中VEGF的表达低于AGA组,sFlt-1的表达水平高于AGA组,差异有统计学意义(χ2=8.44,P=0.04)。②胎盘组织中VEGF的表达水平与胎儿出生体重呈正相关(r=0.427,P<0.01),胎盘组织中sFlt-1的表达水平与胎儿出生体重呈负相关(r=-0.569,P<0.01)。结论孕妇胎盘组织中VEGF及sFlt-1表达水平的变化可能与胎儿出生体重有关。     

Insulin-like growth factor binding protein concentration and post- translational modification in embryological fluid

Levels of proteolytic activity directed against insulin-like growth factor binding protein 3 (IGFBP-3) and the distribution of phosphorylated isoforms of IGFBP-1 were assessed in matched sample sets of maternal serum, coelomic fluid and amniotic fluid from 21 pregnancies at 6-12 weeks gestation. In addition, concentrations of immunoreactive IGFBP-1 to -3, insulin-like growth factor (IGF)-I and - II were determined in all three compartments in 21 pregnancies, and in coelomic fluid and maternal serum in 58 pregnancies. IGF-I concentrations were highest in maternal serum and similarly low in coelomic and amniotic fluid. IGF-II concentrations were also highest in maternal serum but easily detectable in coelomic fluid where concentrations showed a significant correlation with gestational age. IGFBP-1 concentrations were higher in coelomic fluid than in either maternal serum or amniotic fluid and showed a significant correlation with gestational age in this compartment. Analysis of IGFBP-1 phosphoforms showed clear differences in phosphorylation of IGFBP-1 between groups with maternal serum containing predominantly the phosphorylated forms and coelomic fluid almost exclusively the non- phosphorylated form. First trimester amniotic fluid IGFBP-1 was barely detectable and appeared non-phosphorylated. These findings suggest that the high IGF-II concentrations and lack of inhibitory phosphoforms of IGFBP-1 in coelomic fluid could potentially enhance mitogenic activity in the early human gestational sac. IGFBP-2 concentrations were high in coelomic fluid compared with maternal serum whereas coelomic fluid IGFBP-3 concentrations were intermediate, easily detectable and correlated strongly with gestational age. Protease activity was far less in coelomic fluid than in matched maternal serum samples. Marked differences in both concentrations and post-translational modification of IGFBPs in maternal serum compared with embryonic fluid suggest different regulatory pathways.      

促酰化蛋白水平与胎儿生长发育的关系研究

目的探讨脐血促酰化蛋白（ASP）水平与胎儿生长发育的关系。方法研究对象为大于胎龄儿（LGA）、适于胎龄儿（AGA）和小于胎龄儿（SGA）各30例。应用ELISA法测定血清和羊水ASP浓度、血清脂联素浓度,RIA法测定血清胰岛素和瘦素水平,用免疫比浊法测定血脂水平;并分析脐血ASP水平与母血和羊水ASP水平、胎盘重量、新生儿身长、性别、体质量、BMI、腰围、腰臀比、血脂、胰岛素、瘦素和脂联素水平,孕妇的体质量和BMI、血脂水平的相关性。结果①LGA的脐血ASP水平高于AGA,AGA的脐血ASP水平高于SGA,差异有统计学意义（P〈0.001）;三组新生儿血脂水平差异无统计学意义（P〉0.05）。②脐血ASP水平与新生儿出生体质量、身长、BMI、腰围、腰臀比、胰岛素、瘦素、脐血甘油三酯水平呈显著正相关（P〈0.001）,与血脂联素水平呈显著负相关（P〈0.001）,与母血和羊水ASP水平、胎盘重量无相关性（P〉0.05）。③男、女婴脐血ASP、血脂各成分水平比较差异均无统计学意义（P〉0.05）。结论促酰化蛋白参与胎儿生长发育调节,脐血ASP水平可反映胎儿的生长发育状况。     

Birth weight in pre-eclamptic and normotensive twin pregnancies: an analysis of discordance and growth restriction

The aim of this study was to verify whether twin pregnancies complicated by pre-eclampsia were associated with a higher rate of inter-twin weight discordance or an increased prevalence of small for gestational age (SGA) neonates than in normotensive twin pregnancies. A 17 year retrospective study was undertaken by examining 76 twin pregnancies complicated by pre-eclampsia and comparing them with 400 normotensive twin pregnancies. The case notes were reviewed in reference to birth weight differences, birth order, pregnancy outcome and inter-twin birth weight discordance. Statistical analyses were performed with t-test, contingency tables, regression curves, rank sum test and non-parametric survival plots. Power analysis was also carried out. Pre-eclamptic twin pregnancies were delivered at similar weeks of gestation to normotensive. They resulted in a smaller size for the second twin the earlier the delivery week, while in normotensive twin pregnancies no significant difference occurred at any week. Twin pregnancies complicated by pre-eclampsia showed higher rates of SGA neonates among second twins than those with normal pressure. The >25% discordance was associated with lower gestational age at delivery in each group [mean (range) 33 weeks (27-38) versus 37 (29-41), P < 0.005 pre-eclampsia and 35 weeks (25-41) versus 38 (25-42), P < 0.001 normotensive]. In pre-eclampsia the concomitant occurrence of SGA second twin and the discordance >25% was associated with shorter gestation while the presence of SGA second twin alone was not.     

Genes or placenta as modulator of fetal growth: evidence from the insulin-like growth factor axis in twins with discordant growth

To determine whether fetal growth is regulated by placental and/or fetal factors, we measured maternal and fetal concentrations of insulin-like growth factor-I (IGF-I), IGF-II and insulin-like growth factor binding protein-1 (IGFBP-1) (total and non-phosphorylated) in dichorionic (DC) and monochorionic (MC) twins with (DC, n = 13; MC, n = 12) or without (DC, n = 13; MC, n = 12) discordant birth weight. In the discordant MC pregnancy, growth-restricted (IUGR) twins had lower IGF-II concentrations (P < 0.001) but similar IGF-I concentrations compared to the appropriate for gestational age(AGA) co-twin. The differences in IGF-II concentrations showed a positive association with percentage birth weight discordance (r = 0.60; P < 0.05) in MC twins. In contrast, IUGR DC twins had lower IGF-I concentrations (P < 0.05) but similar IGF-II concentrations compared to the AGA co-twins. There was a positive correlation between IGF-I concentrations and birth weight (r = 0.47; P < 0.05) in DC twins. Total IGFBP-1 concentrations were higher in both MC and DC IUGR twins (P < 0.05) compared to AGA twins. A negative association was found between total IGFBP-1 concentrations and birthweight of both MC (r = 0.47; P < 0.05) and DC (r = 0.58; P < 0.01) twins. No such differences in IGF concentrations were found between concordant MC and DC twin pairs. The maternal IGF concentrations were comparable between the MC and DC groups. These data suggest that growth discordances of twins exposed to the same maternal environment may be due to variations in either IGF-I or IGF-II/IGFBP-1, depending upon the functioning of the placenta.     

Comparison of fetal growth in singleton, twin, and triplet pregnancies.

The objective of this longitudinal retrospective study was to evaluate differences of the fetal growth and fetal organ growth among singleton small for gestational age (S-SGA), singleton appropriate for gestational age (S-AGA), twin (Tw-AGA), and triplet (Tri-AGA) infants. Ultrasonographic examinations were performed on 35 S-AGA, 18 S-SGA, 52 Tw-AGA and 12 Tri-AGA fetuses. Circumferences of head (HC), abdomen (AC), spleen (SC) and adrenal gland (AGC) and lengths of femur diaphysis (FDL), liver (LL), estimated weight (EWT) were measured every 2 weeks after 15 weeks of menstrual age until delivery. There was no significant difference in predicted HC values in S-AGA, Tw-AGA and Tri-AGA fetuses; these values were lowest in S-SGA fetuses. As the number of fetuses in the uterus increased with advancing menstrual age, the slope of the growth curve for predicted AC value became lower, but there was no significant difference between Tri-AGA and S-SGA fetuses. There was no significant difference in predicted FDL values among Tw-AGA, Tri-AGA and S-SGA fetuses; those values were significantly lower than that in S-AGA fetuses. There was no significant difference in predicted EWT value between Tw-AGA and Tri-AGA fetuses, which were intermediate between those for S-AGA and S-SGA fetuses. There were no significant differences in predicted SC and AGC values between S-AGA and Tw-AGA fetuses, respectively. However, in S-SGA fetuses, the slopes of the growth curve for SC and AGC were lower than those in the other two groups with advancing menstrual age. There were slight differences in predicted LL values between S-AGA, S-SGA and Tw-AGA fetuses. These results suggest that in AGA fetuses, there was a slight difference in growth pattern among singleton, twin, and triplet pregnancies.     

脐血促酰化蛋白水平测定与胎儿发育临床意义研究

目的探讨脐血促酰化蛋白(ASP)水平与胎儿生长发育的关系。方法研究对象为大于胎龄儿(LGA)、适于胎龄儿(AGA)和小于胎龄儿(SGA)各30例。应用酶联免疫吸附法(ELISA)测定血浆促酰化蛋白和脂联素浓度,用免疫比浊法测定甘油三酯(TG)、总胆固醇(TCH)、低密度脂蛋白-胆固醇(LDL-c)、高密度脂蛋白-胆固醇(HDL-c)的水平;并分析脐血促酰化蛋白水平与脐血脂联素水平、母血促酰化蛋白水平、新生儿性别、出生体质量、体质量指数、胎盘重量和血脂水平的相关性。结果①LGA的脐血ASP水平高于AGA,AGA的脐血ASP水平高于SGA,差异有统计学意义(P<0.001),三组新生儿血脂水平差异无统计学意义(P>0.05)。②脐血ASP水平与新生儿出生体质量、BM、I脐血甘油三酯水平呈显著正相关(P<0.001),与血脂联素水平呈显著负相关(P<0.001),与母血ASP水平、胎盘重量无相关性(P>0.05)。③男、女婴脐血ASP、血脂各成分水平比较差异均无统计学意义(P>0.05)。结论促酰化蛋白参与胎儿生长发育调节,脐血ASP水平可反映胎儿的生长发育状况。     

Frequency of neonatal hypoglycemia in large for gestational age infants of non-diabetic mothers in a community maternity hospital

Large for gestational age (LGA) infants are at increased risk for hypoglycemia. The aim of the study was to determine the frequency of neonatal hypoglycemia in LGA infants of non-diabetic mothers in a Community Maternity Hospital in Gaziantep, Turkey. Hospital records of 5229 infants of non-diabetic mothers were examined retrospectively. Newborns with birth weight more than 4000 g were defined as LGA. The control group consisted of 100 appropriate for gestational age (AGA) newborns. Capillary blood glucose was measured at the second hour of life. Glucose values lower than 40 mg/dL (2.2 mmol/L) were defined as hypoglycemia. Ninety-six (1.8%) of the 5229 infants were found to be LGA. The mean capillary glucose levels of the LGA newborns were significantly lower than those of the AGA newborns (54 mg/dL (3.0 mmol/L) vs. 95 mg/dL (5.2 mmol/L), p < 0.0001). Neonatal hypoglycemia was established in 16 of 96 LGA infants (16.7%). In the control group hypoglycemia was absent. The rate of hypoglycemia in LGA infants was significantly higher than the rate in the AGA infants (p = 0.0000). As hypoglycemia is not rare in LGA infants and can have serious consequences, blood glucose levels should be screened routinely in LGA infants.     

小于胎龄儿脐血脂联素水平测定及其临床意义

目的探讨小于胎龄儿（SGA）脐血脂联素（APN）水平变化及其对新生儿的影响。方法研究对象为SGA和适于胎龄儿（AGA）各30例。采用放射免疫分析法测定脐血和产妇血脂联素水平。用免疫比浊法测定三酰甘油（TG）,总胆固醇（TCH）,低密度脂蛋白胆固醇（LDL-C）,高密度脂蛋白胆固醇（HDL-c）水平。并分析脐血脂联素水平与母血脂联素,体质量指数（IBM）,胎盘重量和血脂水平的相关性。结果1.SGA脐血脂联素水平低于AGA差异有显著性（P〈0.01）;SGA血TG,TCH,LDL-c,HDL-c水平与AGA比较差异均无显著性（P〉0.05）。2.SGA血清脂联素水平与新生儿身长,新生儿体质量指数BMI,胎盘重量,脐血TG呈显著正相关（r=0.386,0.431,0.365,0.231,P〈0.05）,与母血脂联素水平,孕前和分娩时产妇IBM无相关性（P〉0.05）。结论小于胎龄儿具有较低血清脂联素水平,测定脐血脂联素水平有助于判断SGA的发展趋势。     

Embryo reduction of multifetal pregnancies following assisted reproduction treatment: a modification of the transvaginal ultrasound-guided technique

First-trimester transvaginal embryo reduction is an effective alternative for the management of multifetal pregnancy in assisted reproduction. We have modified the transvaginal technique by performing an intracardiac embryo puncture until asystolia is verified, without the injection of any substances. Any aspiration of embryo tissues or amniotic fluid was avoided. A total of 149 multifetal pregnancies was reduced to twins (n = 134) or singletons (n = 15) at early gestational age (7.8 +/- 0.8 weeks). Eleven cases (7.3%) of miscarriage, two cases (1.3%) of chorioamnionitis, and 17 cases (11.4%) of transient spotting were recorded as postoperative complications. Vanishing of one embryo occurred in four cases (3.0%) of those reduced to twins. The baby take-home rate was 89.5% for twins and 80.0% for singletons. Pregnancy outcome was analysed and compared with a control group of women with non-reduced multiple pregnancies. The birth weight of singleton pregnancies after reduction was lower (2929 +/- 160 versus 3291 +/- 422 g; P < 0.02). These studies show that early transvaginal intracardiac embryo puncture is an effective and safe technique.     

胎盘胰高血糖素样肽-1水平与胎儿出生体重关系的研究

目的探讨胎盘胰高血糖素样肽-1(GLP-1)水平与胎儿出生体重的关系。方法采用免疫组织化学SABC法检测30例分娩正常出生体重儿组(AGA组)、28例高出生体重儿组(LGA组)及28例低出生体重儿组(SGA组)胎盘组织中GLP-1的表达水平。结果①LGA组胎盘组织中GLP-1的表达水平低于AGA组,差异有统计学意义(P<0.05)。SGA组胎盘组织中GLP-1的表达水平高于AGA组,差异有统计学意义(P<0.05)。②胎盘组织中GLP-1的表达水平与胎儿出生体重呈负相关(r=-0.454,P<0.05)。结论胎盘组织中GLP-1表达水平的变化可能在胎儿出生体重的调节中起重要作用。     

Clinicopathological correlation of large-for-gestational age placenta in pregnancies with pregestational diabetes

Studies have demonstrated an association between pregestational diabetes (preGDM) and a higher prevalence of large-for-gestational age placentas (LGA). However, frequency of placental pathologies and perinatal outcomes in LGA placentas is lacking. We aimed to determine differences in perinatal outcome or placental pathology between LGA placentas and appropriate-for-gestational age (AGA) placentas from pregnancies complicated by preGDM. We found LGA placentas are associated with significantly higher neonatal weight but lower fetal-to-placental weight ratio (f/p) for both T1DM and T2DM. T2DM LGA placentas possessed a significantly higher prevalence of placental insufficiency (f/p<10^th percentile). Compared to LGA groups, more chronic villitis were seen in the AGA T2DM group, and more acute chorioamnionitis in the T1DM AGA group. No significant differences were seen in maternal BMI or glycemic control. In pregnancies complicated with preGDM, LGA placentas had generally lower placental efficiency than AGA placentas.     

Do gestational age and weight for gestational age predict concordance in parental perceptions of infant temperament?

Objective To study whether infant weight for gestational age,and gestational age predict mother- and father-rated infanttemperament (IBQ) at 6 months. Methods The sample comprisedof family units with both biological parents and infants bornat term (n = 152). Data on weight and gestational age were collectedform obstetric database. Results Infants born small for gestationalage (SGA) (weight < 10th percentile for gestational age)were rated by both parents as significantly more fearful andnegatively reactive compared to infants born appropriate forgestational age (AGA). Infants born SGA defined by using thelowest 15th or 20th percentile groups did not differ from AGAgroup in temperament. The weekly continuum of gestational agepredicted differences in parental ratings of infant temperamentalattentiveness. Conclusions The predictive significance of infantweight for gestational age and gestational age for behavioraloutcomes appear true also for infants born at term. Concordancein parental perceptions of an infant born SGA emphasizes theclinical significance of the findings.     

Placental villitis and intrauterine growth retardation in a Swedish population

Villitis was studied in placentas from 445 singleton infants from an ethnically homogeneous population with a good socioeconomic standard. There were 161 infants small for gestational age (SGA) and 284 appropriate for gestational age (AGA). Villitis was found in 12 SGA-placentas (7.5 per cent) and 8 AGA placentas (2.8 per cent) (p less than 0.05). The degree of villitis was also related to growth retardation (p less than 0.05). Except for one placenta with villitis due to CMV infection, the cause of villitis could not be determined. No association was found with various studied factors such as hypertension, pre-eclampsia, smoking or maternal pyrexia during pregnancy.     

Asthma medication use in pregnancy and fetal growth

BACKGROUND: Given the high prevalence of asthma in pregnancy, it is important to understand the relationship between asthma medications and fetal growth in the context of appropriate treatment. OBJECTIVE: This study examines the effect of inhaled corticosteroids, systemic corticosteroids, and beta(2)-agonists on fetal growth in 654 infants born to women with asthma compared with 303 infants born to controls without asthma. METHODS: Subjects for this prospective study were enrolled throughout North America between 1998 and 2003 and followed up by the Organization of Teratology Information Services. Incidence of small for gestational age (SGA) infants and mean birth size measures were compared among groups. RESULTS: Mean birth weight of full-term infants born to mothers who used systemic corticosteroids (3373 g) was lower than in the beta(2)-agonist group (3552 g) and controls without asthma (3540 g; P < .05) after adjustment for other risk factors. However, no differences in the incidence of SGA for weight were observed among groups. Adjusted mean birth length was slightly shorter in the systemic steroid group compared with controls (P=.02). Incidence of SGA for length and head circumference and mean head circumference did not vary among groups (P>.05). CONCLUSION: The treatment of asthma with systemic corticosteroids resulted in a deficit of about 200 g in birth weight compared with controls and exclusive beta(2)-agonist users and no increased incidence of SGA. These results suggest that asthma management with beta(2)-agonists and/or inhaled corticosteroids during pregnancy does not impair fetal growth, whereas systemic corticosteroids have a minimal effect which should be weighed against the necessity to control severe asthma.