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Meta-analysis of the effect of intravenous prophylactic ibuprofen on prevention of patent ductus arteriosus in preterm infants

Yunfen QIU ; Zongtai FENG ; Zhijun LU

Chinese Journal of Perinatal Medicine.2010;13(6):488-493. doi:10.3760/cma.j.issn.1007-9408.2010.06.011

Objective To determine the effectiveness and safety of prophylactic intravenous ibuprofen compared to placebo/no intervention on the prevention of patent ductus arteriosus(PDA) in preterm infants.Methods Randomized controlled trials(RCT) or quasi-RCT comparing prophylactic intravenous ibuprofen versus placebo/no treatment for prevention of PDA in preterm infants were enrolled. The standard search strategy included electronic search and manual search. Electronic search was carried out in databases including PubMed,ScienceDirect, EMBASE, OVID, Cochrane Library, VIP Chinese Periodical Database and Chinese Digital Hospital Library (www. chkd. cnki. net) without language restriction. As a supplementation,references in previous reviews and studies identified as relevant had been examined by manual search. RevMan 5.0. 21 was used in the statistical analysis. Effects were expressed as weighted mean difference (WMD) and 95% confidence interval (CI) for continuous data while risk ratio (RR) and 95%CI for categorical data.Results Four studies qualified for this meta-analysis including three graded 4 and one graded 3 with Jadad scale. Prophylactic use of ibuprofen significantly decreased the incidence of PDA on day three (RR=0. 40,95 % CI: 0. 31-0. 51, P＜0.01 ), the need for rescue treatment with cyclo-oxygenase inhibitors (RR = 0. 18,95 % CI:0. 07-0. 45, P = 0. 0003) and the need for surgical ligation (RR = 0. 34,95 % CI: 0. 14-0. 81, P =0. 02) in the prophylactic group. No significant difference of pulmonary, cerebral, gastrointestinal, and renal complications were found between the prophylactic and control groups. Conclusions Prophylactic intravenous ibuprofen significantly reduces the risk of PDA on day three, decreases the need for rescue treatment with cyclo-oxygenase inhibitors and surgical ligation without significant pulmonary, cerebral,gastrointestinal, and renal complications were seen in the prophylactic group. Due to the limits of evidences to date, prophylactic ibuprofen intravenously for prevention of PDA in preterm infants is not recommended.

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A case-control study on association between antenatal exposure to magnesium sulfate and patent ductus arteriosus in preterm infants

Wenqing YANG ; Changyi YANG ; Hanqiang CHEN

Chinese Journal of Perinatal Medicine.2010;13(6):483-487. doi:10.3760/cma.j.issn.1007-9408.2010.06.010

Objective To identify the association between antenatal exposure to magnesium was conducted on 93 preterm infants with PDA and 93 cases of matched controls without PDA hospitalized in our neonatal intensive care unit between January 2008 and December 2009. Information on antenatal exposure to magnesium sulfate, neonatal birth weight and other perinatal factors was collected and analyzed with univariate analysis, multivariate Logistic regression analysis. Results There were 51 preterm infants exposed to magnesium sulfate antenatally in PDA group and 34 infants in controls. The median (P25-P75) level of neonatal serum magnesium in PDA cases was 0.98 mmol/L (0. 92-1.32 mmol/L),significantly higher than that in controls [0. 90 mmol/L(0. 82-1.09) mmol/L](Z = 3.56, P=0.00). Logistic regression analysis showed that PDA in preterm infants was significantly associated with antenatal magnesium sulfate exposure(OR= 2. 646,95 %CI: 1. 356-5. 163,P=0.004), fetal distress (OR=7. 189, 95% CI:1. 209-42. 756, P=0. 030), neonatal birth weight (OR = 1. 842,95 % CI:1. 087-3. 438, P = 0. 049 ), respiratory failure (OR = 3. 499,95 % CI:1. 256-9. 752, P=0. 017)and postnatal oxygen inhalation (OR=0. 482,95% CI:0. 233-0. 999, P=0. 045).Also, a significant positive correlation was found between PDA and the dose of magnesium sulfate and the concentrations of serum magnesium in preterm infants (x2trend =7. 41, P=0.007; x2trend = 12. 13, P=0.000).Conclusions Antenatal exposure to magnesium sulfate might increase the risk of PDA in preterm infants.

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Severe hyperglycemia during pregnancy and early overfeeding induce metabolic syndrome in adult offsprings in rats

Chanjuan ZENG ; Jingmei MA ; Huixia YANG

Chinese Journal of Perinatal Medicine.2010;13(6):444-449. doi:10.3760/cma.j.issn.1007-9408.2010.06.002

Objective To explore the metabolic phenotype of the adult offspring rats with maternal severe hyperglycemia during pregnancy and overfeeding in early life. Methods The adult Wistar rats were administered intraperitoneally with 20% Streptozotocin (STZ, 50 mg/kg) on day 5 of pregnancy to induce severely gestational diabetes mellitus (SDM) model (blood glucose ≥20 mmol/L). Early postnatal overfeeding models were established through reduction of the number of newborn rats fed by one mother rat. Offsprings were divided into 3 groups according to maternal blood glucose level during the pregnancy and feeding patterns during the lactation period (1) control pups (CP) :maternal euglycemia was achieved during pregnancy and eight pups fed by one mother rat; (2)SDM-normal feeding group: SDM mothers and 8 pups fed by one mother rat;(3)SDM-overfeeding group:SDM mother and 4 pups fed by one mother rat. All pups were fed by standard laboratory chow adlibitum after weaning at 3 weeks of age. The body weight of all pups were measured weekly after weaning. At the age of 26 weeks, the systolic blood pressure (SBP), diastolic blood pressure (DBP) ,heart rate (HR) and metabolic markers, including fasting plasma glucose (FPG), fasting insulin (FINS), total triglyceride (TG), total cholesterol (TC), low density lipoprotein-cholestrol (LDL-C)and high density lipoprotein-cholestrol (HDL-C) were measured in all 3 groups. ANOVA and LSD test were applied in statistical analysis. Results The average plasma glucose level was significantly higher in the SDM mothers than in the controls [(28.34±5.14) mmol/L va (6.25±1.41) mmol/L,P＜0.05]. After weaning at 3 weeks, the weight of SDM-overfeeding group and SDM-normal feeding group was lighter than that of CP group [(43.63±4.83) g, (31.45±10.21) g vs (55.75±8.41) g,P＜0. 05], meanwhile, that of the SDM-overfeeding group were heavier than that of the SDM-normal feeding group (P＜0. 05). Pups in SDM-overfeeding group exhibited catch-up growth during the lactation period, and those in SDM-normal group showed catch-up growth at both lactation period and childhood. At 26 weeks of age, the systolic blood pressure and TG level of pups in SDM-normal feeding and overfeeding group were (153.31 ± 13.91) mm Hg and (147.21 ± 12.29) mm Hg, and (0. 73±0. 22) mmol/L and (0. 71±0.49) mmol/L, respectively, which were higher than those of the CP group [( 132.21 ± 11.26) mm Hg, and (0. 37 ± 0. 08) mmol/L, P＜0.05], but no significant difference was found between the two SDM groups (P＞0.05). There was no difference in FPG levels among the three groups, but the FINS level and HOMA-IR in the SDM-overfeeding group were higher than in the SDM normal feeding and CP group [( 12. 552 ± 3.260) mU/L vs (9.067 ± 1.782) mU/L and (8.590± 0.806) mU/L, 2.400± 0.624 vs 1.797 ± 0.508 and 1.729 ± 0.246; P＜0.05].Conclusions Fetal exposure to maternal severe hyperglycemia during pregnancy may lead to low birth weight infant who will exhibit postnatal catch-up growth. This may lead to the increased risk of metabolic syndrome in the offspings when they grow up, and this process would be accelerated by early overfeeding.

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Follow-up of cardiac function in infants of mothers with gestational diabetes mellitus

Chen CHU ; Yonghao GUI ; Yunyun REN ; Weida CHEN ; Xiaotian LI

Chinese Journal of Perinatal Medicine.2010;13(6):456-462. doi:10.3760/cma.j.issn.1007-9408.2010.06.004

Objective To follow up the changes of postnatal cardiac sizes and function in infants of mothers with gestational diabetes mellitus (GDM). Methods Eighteen GDM mothers with euglycemia (GDM group) and 24 gestational age-matched normal pregnant women (control group),having prenatal examination and delivered in Women's Hospital of Fudan University from January to August in 2007, received fetal echocardiographic examination in late pregnancy. Infants of these GDM mothers and 24 age-matched healthy infants of normal pregnancy (control group) received sonographic follow up. Cardiac sizes and function were evaluated and compared. Results At birth, there were six (33.3%) infants of large for gestational age (LGA) and 12(66.7%) appropriate for gestational age(AGA) in GDM group, while in the control group, there were two LGA (8. 3%) and 22(91.7%)AGA infants (x2 =3. 840, P= 0. 05). Both the interventricular septum and left ventricular walls in GDM fetuses were thicker than in control fetuses (P ＜ 0.05). No increase in the thickness of ventricular walls was observed till infantile period. However, the end-systolic thickness of left ventricular walls in LGA infants was still larger than in control infants [(4.55 ± 0.37) mm vs (4. 13±0.39)mm, P＜0. 05], and end-diastolic left ventricular long-diameters were also larger [(37. 3±2.3) mm vs (34.6±2.6) mm] (P＜0. 05). In GDM fetuses, the peak velocities of aorta and pulmonary artery and left cardiac output were higher than in the controls (P＜ 0. 01 ), and right/left cardiac outputs ratios were lower (1.198±0.206 vs 1. 430±0. 321, t= -2.668,P=0. 011). Till infantile period, only right/left cardiac outputs ratios in AGA infants of GDM group were larger than in controls (P＜0. 05). GDM fetuses' left atrial shortening fraction and tricuspid E/A ratios were smaller (P＜0. 05). In infantile period, only left atrial shortening fraction in GDM infants was still smaller than in controls (0. 356 ± 0. 040 vs 0. 386 ± 0. 041, t = - 2. 332, P = 0. 025). Left and right ventricular Tei index in GDM fetuses were 0. 482±0. 129 and 0. 414±0. 094, both larger than those of control fetuses (0. 309 ± 0. 074 and 0. 283 ± 0. 072) (t = 5. 075 and 5. 129, P = 0. 000 ). Till infantile period they both became significantly lower and no differences were found among LGA, AGA and control infants. Conclusions The cardiac sizes and function at 2-3 months of age, in infants of GDM mothers with good glucose control, became better than that in uterus.

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Changes of serum estradiol in newborns and the relationship with retinopathy of prematurity

Juan DU ; Wenjing SHI ; Chao CHEN

Chinese Journal of Perinatal Medicine.2010;13(6):478-482. doi:10.3760/cma.j.issn.1007-9408.2010.06.009

Objective To observe the serum estradiol level in newborns at different gestational age and the infants with retinopathy of prematurity (ROP), and explore the relationship between these changes and ROP. Methods A total of 178 newborns hospitalized in the Children's Hospital of Fudan University were enrolled in the study. They were divided into three groups based on the gestational age, ＜ 32 weeks group, 32-37 weeks group and term group. The three groups were further divided into non-oxygen and oxygen subgroups. Infants with birth weight less than 2000 g were evaluated for ROP and those diagnosed as ROP were under ROP group (n=6). Serum estradiol levels were measured every week from birth to discharge with radioimmunoassay. Results Serum estradiol levels of newborns quickly declined after birth. In the non-oxygen subgroups, serum estradiol levels in 32 ～ 37 weeks group were remarkably higher than those of term group in the first week [(3506±1376) pmol/L vs (1717±179) pmol/L,P＜0. 05] and the third week [(1431±92) pmol/L vs (996±102) pmol/L, P＜0. 05]; Serum estradiol levels in ＜32 weeks group was only remarkably higher than those of term group in the first week [(3173± 1369) pmol/L vs (1717± 179) pmol/L,P＜0. 05]; Serum estradiol level in the ＜32 week group was (560±355) pmol/L, lower than that in the 32-37 weeks group [( 1124 ± 128) pmol/L] (P＜0. 05). There was no difference of serum estradiol levels in the oxygen and non-oxygen subgroups of the same group. There was no significant difference of serum estradiol levels between the ROP group and ＜32 weeks group. Serum estradiol levels in ROP group was lower than that of premature group without ROP at 29 and 32-36 weeks of corrected gestational age, but no statistical difference was shown. Conclusions Very low serum estradiol level in premature infants may be related to the development of ROP, but further clinical studies are required.

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Influence of maternal glucose metabolism during pregnancy and family history of diabetes on insulin sensitivity in infants and toddlers

Taoran FU ; Xuemei WANG ; Xinli WANG ; Xiaomei TONG

Chinese Journal of Perinatal Medicine.2010;13(6):450-455. doi:10.3760/cma.j.issn.1007-9408.2010.06.003

Objective To explore the related factors of insulin sensitivity in infants and toddlers. Methods From January 2006 to May 2008, 246 infants and 120 toddlers who had regular physical check-ups at the Children Healthcare Center of Third Hospital of Peking University were selected in this retrospective study. The homeostasis model assessment insulin resistance index (HOMA-IR), insulin action index(IAI), fasting glucose-to-insulin ratio (FGIR) and HOMA-β cell function (HOMA-β) were measured with the homeostasis model analysis. According to different glucose metabolic situation of the pregnant mothers and diabetes family history, the infants and toddlers were divided into different groups. The above indicators were compared among groups.Results In infants with maternal diabetes, the levels of HOMA-IR and HOMA-β were 3.24 (2.76-4.12) and 164. 00 (114. 44-192.85), higher than those born to mothers without abnomal glucose metabolism [1.51 (0. 86-2.50) and 67.07 (41.83-106.22)], while the levels of IAI and FGIR were lower[-7.18(-7.41-7.02) and 7.31(5.82-8.55) vs -6.41(-6.92-5.85) and 14.84(9.49-24. 79)] (Z=3. 76,3. 35,3. 76 and 3.71, P＜0. 017). Compared with infants of maternal impaired glucose tolerance,the level of HOMA-IR was higher (Z= 3.19, P＜0.017) in infants with maternal diabetes,the level of IAI was lower(Z= 3. 19, P＜0. 017). No significant difference of insulin sensitivity were observed between infants with and without maternal impaired glucose tolerance (P＞0. 017). The level of HOMA-IR was higher in infants and toddlers with diabetes in first-degree relatives [infants: 3.24(2. 73-4. 13) vs 1.41(0.84-2.50) ; toddlers: 3.98(2.62-4.80) vs 1.70(0.92-3.04); P＜0. 017], while the levels of IAI and FGIR were lower [infants: IAI, -7. 18(-7.42-- 7.00) vs - 6.34 ( - 6.91- 5.82); FGIR, 7.31 (5.40-7.48) vs 14.87 (9.53-25.17); toddlers: IAI,-7.38(-7.57-6.97) vs -6.54(-7.11-5.92); FGIR, 6.17(6.04-8.00) vs 12.65(8.33-21.53), P＜0. 017], and the level of HOMA-β was higher just in the infants [164.00(137.82-198.00) vs 67.06(40.40-106.83), P＜0. 017]. No significant difference was observed in infants with second-degree relatives diabetes and without diabetic family history group (P＞0. 017). Conclusions Maternal diabetes and diabetic family history in first-degree relatives were significantly related to the decrease of insulin sensitivity in infants and toddlers.

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Antenatal factors associated with birth weight of twins and risk factors for discordant twins

Hongying HOU ; Zhenyan HAN ; Jianhui FAN ; Qicai PENG ; Qun FANG

Chinese Journal of Perinatal Medicine.2010;13(6):494-498. doi:10.3760/cma.j.issn.1007-9408.2010.06.012

Objective To investigate the antenatal influencing factors associated with birth weight of twins and the risk factors for the occurrence of discordant twins. Methods Totally, 834 twins delivered at the Third Affiliated Hospital from January 2000 to December 2009 and the First Affiliated Hospital of SUN Yat-sen University, from January 2000 to June 2009, were recruited in the study. The diagnosis criteria of discordant twins was intrapair birth weight difference more than 25 %.Antenatal factors on birth weight were retrospectively investigated among twins and discordant twins respectively with Logistic analysis. Results (1) There were several factors associated with birth weight of twins, including maternal age, conceptive style, chorionicity, gestational diabetes mellitus and placental cord insertion ( P = 0. 021, 0. 000, 0. 000, 0. 012 and 0. 017, respectively). While hypertensive disorder in pregnancy, parity and fetal gender differences were not associated with the birth weight of twins (P＞0.05). Hypertensive disorder in pregnancy (OR=2. 600, 95% CI:1. 566-4. 316) and monochorionicity (OR= 1. 833, 95% CI: 1.010-3. 582) were risk factors of discordant twins. All 834 twin pregnancies were divided into 4 groups according to materal age, ＜25 yrs (n=69), 25-30 yrs (n=312), 30-35 yrs (n=325) and ≥35 yrs (n=128). The average birth weight of twins were (2205±483) g, (2347±406) g, (2381±439) g and (2352±455) g. Significant difference was found bewteen every two groups (P＜0. 05) except that between the 30-35 yrs and ≥35 yrs group (P＞0.05). Among twins of different gender (n=270), the average birth weight of boys and girls were (2416±-514) g and (2322±488) g, and that of female twins (n=272) and male twins (n=292) were (2301±418) g and (2381±428) g. Significant difference was shown between every two groups (P＜0.05) except that between the male twins and male fetus of twins of different gender (P＞0.05).Conclusions The fetal birth weight of twins decreases remarkably when maternal age ＜25, or monochorionicity twins, or complicated with marginal or velamentous placental cord insertion or female pairs.However, birth weight of twins would increase if the pregnancy conceived by assisted reproductive technology or complicated with gestational diabetes mellitus. Twin pregnancy complicated with hypertensive disorder in pregnancy or monochorionicity should alert the clinicians of discordance twins.

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Insulin level in human milk and its associated factors

Yaping LUO ; Xiujing SUN ; Danhua WANG

Chinese Journal of Perinatal Medicine.2010;13(5):375-378. doi:10.3760/cma.j.issn.1007-9408.2010.05.008

Objective To determine the human milk insulin(HMI) concentrations of healthy,gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT) lactating mothers and their correlative factors and to explore the effect of HMI on growth and development of neonates. Methods HMI of colostrum and mature milk collected from 148 healthy lactating mothers and 46 GDM/GIGT mothers were determined by radioimmnuoassay. The intergroup HMI levels were compared by Wilcoxon test. Results (1) In the GDM/GIGT group, colostrum HMI was 28.81 μU/ml(13. 84-43.14 μU/ml), significantly lower than that of mature milk which was 57.50 μU/ml(36. 70-82. 73 μU/ml) (Z=-4. 828,P=0. 000). HMI of mature milk in the healthy group was 35.88 μU/ml(25.91-46.85 μU/ml), lower than in the GDM/GIGT group (Z=-2.874,P=0.004). ( 2 ) The colostrum HMI of the mothers underwent cesarean section was 23.64 μU/ml (14.90-38.51 μU/ml) lower than in the vaginal delivery ones which was 38.89 μU/ml(23.14-65.54 μU/ml)(Z= -4. 510, P= 0. 000). (3) HMI of mature milk in mixed feeding cases was 42.58 μU/ml (26.60-73.06 μU/ml),significantly higher than that of breast feeding ones which was 36.32 μU/ml(26.00-46.16 μU/ml)(Z=-2. 377,P=0.019). (4) Both HMI in colostrum and mature milk were positively correlated with maternal BMI (P＜0.05). Conclusions The mode of delivery significantly affects the HMI in colostrum. GDM/GIGT and the feeding patterns have some effects on HMI levels in mature breast milk. The HMI level is positively correlated with maternal BMI.

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Influence of maternal H1N1 influenza on perinatal outcomes

Jing CHEN ; Caixia LIU

Chinese Journal of Perinatal Medicine.2010;13(5):371-374. doi:10.3760/cma.j.issn.1007-9408.2010.05.007

Objective To discuss the influence of H1N1 influenza on maternal and fetal outcomes and obstetric management. Methods Totally, data were collected on 19 women, affected by H1N1 influenza and admitted to Shengjing Hospital of China Medical University from November 7, 2009 to December 15,2009, and retrospective analysis was performed on the maternal and fetal outcomes. Results Among the 19 cases, three were( 15. 8%, 3/19) in puerperium, who were all mild cases and recovered. Sixteen (84.2%, 16/19)women were diagnosed as H1N1 influenza during pregnancy, among which two in early pregnancy (12. 5%), seven (43. 8%) in mid-term pregnancy and seven (43. 8%) in late pregnancy. According to the severity of H1N1 influenza, six were mild cases (37. 5% ,6/16), two (12. 5% ,2/16)were severe cases and eight (50. 0% ,8/16)were critical. For these 16 pregnant women, thc two cases in early pregnancy (mild cases) were terminated after recovery from H1N1 influenza. Among the seven mid-term cases, four mild and one of the three severe and critical cases delivered till term, and two of the three severe and critical cases were delivered abdominally because of fetal death intrauterine or maternal severe complications at 27 or 23 weeks of gestation. All of the seven late pregnant cases underwent emergent cesarean section due to maternal or fetal reasons, and two fetuses died in the uterus at late pregnancy and five survived including four preterm babies and one full term baby. Altogether, nine cases (56. 3%, 9/16)underwent emergent cesarean section, and six babies born alive and five survived without any symptom of influenza, two women died (10. 5%,2/19) after the operation. Conclusions Pregnant women during late pregnancy infected by H1N1 influenza are susceptible to develop into severe and critical conditions. Termination of the pregnancy in time is effective in both life-saving of the mothers and babies and prevent neonatal infection against H1N1.

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Relationship between transforming growth factor-β1 and interleukin-10 in breast milk and allergic diseases in infants

Jianxing ZHU ; Liya ZHANG ; Huajun LI ; Tongxin CHEN ; Yazhong ZHU ; Shengmei WU

Chinese Journal of Perinatal Medicine.2010;13(5):364-370. doi:10.3760/cma.j.issn.1007-9408.2010.05.006

Objective To verify the relationship between transforming growth factor-β1(TGF-β1) and interleukin-10 (IL-10) in breast milk and allergic diseases development in infants. Methods Totally 191 mothers (99 allergics and 92 controls) and their full-term newborns participated in this prospective study on development of children atopy. Maternal blood, cord blood, colostrum and mature milk were assayed for TGF-β1 and IL-10 by enzyme-linked immunosorbent assay. Infants underwent pediatrician evaluation for allergic diseases at six months old. Concentrations of TGF-β1 and IL-10 from allergic and non-allergic mothers and prevalence of allergic diseases of infants were compared. Results The level of IgE in allergic mothers was 30 750 IU/L(6600-410000 IU/L),lower than that in non-allergic mothers[50000 IU/L(7100-610000 IU/L)](Z=-3. 444,P=0. 001).No difference in the concentration of TGF-β1, IL-10 and IgE in mature milk was observed between allergic and non-allergic mothers. TGF-β1, IL-10 and IgE levels in colostrum of allergic mothers were 2300 pg/ml(620-7000 pg/ml), 12. 8 pg/ml(7.5-560.0 pg/ml)and 7000 IU/L(5100-56000 IU/L),significantly higher than those in non-allergic mothers[1830 pg/ml(1240-9400 pg/ml), 11. 1 pg/ml (7. 2-630.0 pg/ml)and 6700 IU/L(5200-35000 IU/L)] (Z=-2. 215, -2. 730 and -2. 706,P＜0.05).In both allergic and non-allergic mothers, TGF-β1 and IL-10 levels in cord blood were higher than those in maternal blood, while IgE was lower. TGF-βl and IL-10 and IgE levels in colostrum were higher than mature milk(P＜0.05). At six months old, the prevalence of allergic diseases of infants from allergic mothers(59. 6%, 59/99) was significantly higher than those from non-allergic mothers (21. 7%, 20/92)(x2= 28. 177, P= 0. 000). The prevalence of allergic diseases of infants who completed two weeks' colostrum-fed after birth (44.5 %, 73/164) was significantly higher than those who did not (22.2%,6/27)(x2 =4. 749,P-=0. 029). Conclusions High concentration of TGF-βl and IL-10 in colostrum does not show any protective effect against allergic diseases in infants. The prevalence of allergic diseases of colostrum-fed infants is significantly higher than non colostrum-fed infants, showing that colostrum-fed might play a role in allergic diseases development.

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