Just Accepted by The Journal of Maternal-Fetal & Neonatal Medicine
Predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes Dan Wang, Li Zhu, Shulian Zhang, Xueqin Wu, Xiaoli Wang, Qin Lv, Dongmei Gan, Ling Liu, Wen Li, Qin Zhou, Jiarong Lu, Haiying He, Jimei Wang, Hua Xin, Zhankui Li, Chao Chen Doi: 10.3109/14767058.2016.1147549 Abstract OBJECTIVE: We examined the predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes. STUDY DESIGN: This was a multicenter, retrospective cohort study conducted in China. We selected 178,709 singletons weighing ≥ 2,500 g with gestational age 37– 44 weeks. We categorized macrosomia with two gradations (4,000–4,499 g and ≥ 4,500 g) and compared them with a normosomic reference group of infants with birthweight 2,500–3,999 g. RESULTS: The risks of obstetric and neonatal complications increased when infants had a birthweight of ≥ 4,000 g. The rates of infant mortality, Apgar score ≤ 3 at 5 min, respiratory and neurological disorders rose significantly among neonates weighing ≥ 4,500 g. CONCLUSION: A definition of macrosomia as birthweight ≥ 4,000 g could be beneficial as an indicator of obstetric and newborn complications, and birthweight ≥ 4,500 g might be predictive of severe infant morbidity and mortality risk.
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Predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes Dan Wang1, Li Zhu1, Shulian Zhang1, Xueqin Wu2, Xiaoli Wang3, Qin Lv4, Dongmei Gan4, Ling Liu5, Wen Li6, Qin Zhou7, Jiarong Lu8, Haiying He9, Jimei Wang10, Hua Xin11, Zhankui Li12, Chao Chen1* 1
Department of Neonatology, Children’s Hospital of Fudan University, Shanghai, China.
2
Zhejiang Jiaxing The First Hospital, China. 3Shanghai Jiading Maternal and Child Care
Hospital, China. 4Ningbo Women and Children’s Hospital, China. 5Guizhou Maternal and Child Care Hospital, China. 6Qilu Hospital of Shangdong University, China. 7Jiangsu Wuxi
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Maternal and Child Health Care Hospital, China. 8Xinjiang Yili Maternal and Child Care
Gynecology Hospital of Fudan University, China. 12
Obstetrics and
Xinjiang Boertala Hospital, China.
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Shanxi Maternal and Child Care Hospital, China.
11
10
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Hospital, China. 9The Third Hospital of Baotou Steel Group, China.
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* Correspondence to: Chao Chen, No. 399 Wanyuan Road, Shanghai 201102, PR China. E-mail addresses: [email protected] (Chao Chen).
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Tel: 8621-64931990
Abstract OBJECTIVE: We examined the predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes. STUDY DESIGN: This was a multicenter, retrospective cohort study conducted in China. We selected 178,709 singletons weighing ≥ 2,500 g with gestational age 37–44 weeks. We categorized macrosomia with two gradations (4,000–4,499 g and ≥ 4,500 g) and compared them with a normosomic reference group of infants with birthweight 2,500–3,999 g.
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RESULTS: The risks of obstetric and neonatal complications increased when infants had a
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birthweight of ≥ 4,000 g. The rates of infant mortality, Apgar score ≤ 3 at 5 min, respiratory and neurological disorders rose significantly among neonates weighing ≥ 4,500 g.
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CONCLUSION: A definition of macrosomia as birthweight ≥ 4,000 g could be beneficial as
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an indicator of obstetric and newborn complications, and birthweight ≥ 4,500 g might be predictive of severe infant morbidity and mortality risk.
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Keywords: Macrosomia, birthweight, threshold, outcome
Introduction The term “macrosomia” is used to describe an abnormally large fetus or neonate. No consensus has been reached to define macrosomia [1-4]. Macrosomia is variously characterized by birthweight of ≥ 4,000 g, ≥ 4,500 g and ≥ 5,000 g, and is associated with numerous maternal and neonatal complications. For mothers, bearing macrosomia increases risks of cesarean section, prolonged labor, postpartum hemorrhage and third- and fourth-degree lacerations [2]. For neonates, macrosomia is associated with birth trauma,
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perinatal asphyxia, shoulder dystocia and death [4]. Children who have macrosomia at birth
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and were exposed to an intrauterine environment of diabetes or maternal obesity are at an increased risk of developing metabolic syndrome [5]. Therefore, macrosomia has become a
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frequent challenge.
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In recent decades, worldwide, there have been increases in mean birthweight, mean birthweight for gestational age, and the prevalence of large-for-gestational-age (LGA; weight > 90th percentile for gestational age) [1, 2]. In China, investigators also showed an increase in prevalence of macrosomia from 6.0% in 1994, to 7.3% in 2014 [3]. Risk factors that increase
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the possibility of bearing an infant with macrosomia include advanced maternal age, maternal
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height, multiparity, previous macrosomia, maternal obesity, gestational diabetes mellitus (GDM) and male fetus [1-6]. Given that pregnant women are now older, heavier and more likely to have diabetes mellitus than before, this may lead to larger babies [8, 9]. The aim of this study, which used recent multicenter birth data in China, was to determine predictive thresholds for adverse maternal or neonatal outcomes, including maternal complications, neonatal morbidity and infant mortality. Although it is widely
accepted that large birthweight is associated with excess risk of neonatal death, the birthweight cutoffs that signal significant increases in general maternal or neonatal poor outcomes have yet to be determined.
Methods and materials Data We extracted data from the Chinese Neonatal Network, which contains birth records in China,
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covering seven representative geographic areas: North (Hebei, Shanxi and Shandong
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Provinces and Inner Mongolia Autonomous Region); Northeast (Heilongjiang and Liaoning Provinces); East (Jiangsu, Zhejiang and Anhui Provinces and Shanghai city); Central (Henan
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and Hubei Provinces); Southern (Guangdong and Fujian Provinces and Guangxi Autonomous
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Region); Southwest (Sichuan, Guizhou and Yunnan Provinces and Tibet Autonomous Region); and Northwest (Shanxi and Gansu Provinces, and Ningxia and Xinjiang Autonomous Regions). Primary-level hospitals that did not provide obstetric services were excluded from this study. This study was conducted in 23 provinces or autonomous regions
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infants.
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in China from May 2010 to April 2014. A total of 58 hospitals were recruited, with 178,709
Data collection We obtained data from medical records in each participating hospital. All investigators were trained and accredited prior to this survey. Each completed questionnaire was checked by a field supervisor at the provincial level. Data were registered in a specially designed network database by two physicians or midwives independently with automated monitor for
out-of-range values and logic mistakes. The research ethics boards of each participant hospital approved the protocol. Definition Macrosomia was defined as a birthweight of ≥ 4,000 g, regardless of gestational age (GA) [2, 8]. Previous studies suggested that there was a significant difference in adverse birth outcomes between birthweights of 2,500–3,999 g and ≥ 4,000 g [2, 8]. Therefore, we used a birthweight of 2,500–3,999 g and GA of 37–42 weeks as a reference group (142,615 infants
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[79.8%]). Moreover, given that macrosomic infants with birthweight ≥ 4,500 g have an
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increased risk of still birth compared to those with birthweight 4.0–4.49 kg [10], we divided macrosomia into high birthweight group (HBW; birthweight of 4,000–4,499 g, irrespective of
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GA; 10,064 infants [5.6%]) and very high birthweight group (VHBW; birthweight of ≥ 4,500
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g, irrespective of GA; 1,308 infants [0.7%]). The remaining group contained infants with birthweight < 2,500 g, comprising 24,722 births (13.8%). In our analysis of all births, marcosomia risk factors in the correlation data included maternal age, GA at delivery, parity, GDM, obesity, and gender of newborn. Maternal age
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was defined as completed years at time of delivery and classified into two categories: < 35
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years and ≥ 35 years. GA was the time elapsed between the first day of the last normal menstrual period and the day of delivery. If pregnancy was achieved using assisted reproductive technology, GA was calculated by adding two weeks to the age of conception [11]. GA was separated into ≤ 40 and > 40 weeks. Parity was defined as the number of live births before the index pregnancy and divided into primiparity and multiparity. GDM criteria were suggested by the International Association of Diabetes and Pregnancy Study Group [12,
13]. Maternal obesity was characterized by body mass index ≥ 30 kg/m2 [14]. The main maternal characteristics were mode of delivery (including vaginal and cesarean delivery), intervention during delivery (including vacuum extraction and low forceps) and obstetric complications (including cephalopelvic disproportion, labor extension and postpartum hemorrhage). Postpartum hemorrhage was defined as a blood loss of ≥ 500 ml within 24 h after birth, according to the recommendation of the World Health Organization [15]. We defined composite obstetric complication as cephalopelvic
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disproportion, labor extension and postpartum hemorrhage.
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The primary neonatal outcome measures were mortality and hospitalization. Neonatal mortality was assessed by deaths happening in the first 28 days after birth. Neonatal
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hospitalization was the administration to the common neonatal ward or neonatal intensive care
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unit. The secondary outcome measures included Apgar score ≤ 3 at 5 min, birth trauma, hypoglycemia and respiratory and neurological disorders. Hypoglycemia was characterized as blood glucose < 2.6 mmol/L at any time point during the stay in-hospital, irrespective of GA or hour of life. Cephalohematoma and clavicle fracture were classified as birth trauma. Hypoxic
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ischemic encephalopathy (HIE) and intracranial hemorrhage (ICH) were categorized as
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neurological morbidity. We also defined respiratory morbidity as any form of respiratory distress (including aspiration pneumonia and hyaline membrane disease [HMD]) that necessitated admission of the neonate to the common neonatal ward or intensive care unit irrespective of the need for any diagnostic tests or therapeutic intervention. In contrast, respiratory support included the entire spectrum ranging from nasal cannula and neonatal continuous positive airway pressure (CPAP) to mechanical ventilation. Indications for
intravenous fluids included any primary gastrointestinal pathological condition or a nutrition-related disorder, such as feeding intolerance or hypoglycemia. Neonates who needed intravenous fluids for their respiratory or neurological status were also included. Infants with an Apgar score ≤ 3 at 5 min, respiratory and neurological disorders need more medical attentions, therefore, we described these complications as composite severe neonatal disorder. The diagnoses of the above diseases were based on the previous criteria used in China until 2009.
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Statistical analysis
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Statistical analysis was performed with SPSS version 19. Differences in the study parameters between infants with normal birthweight and macrosomia were detected using the χ2 test for
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categorical variables and Student’s t-test for continuous variables. Logistic regression models
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were used to examine the effects of birthweight on maternal and neonatal complications, controlling for maternal age, GA at delivery, delivery mode, infant gender and presence of GDM. We also conducted similar logistic regression models to assess risk factors for macrosomia. For logistic regression models, odds ratios (OR) and 95% confidence intervals
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(95% CI) are expressed. p < 0.05 was the criterion for significance.
Results A total 178,709 singleton deliveries were recorded in 23 provinces in China from May 2010 to April 2014, with a mean birthweight and GA of 3,235 ± 533,6 g and 39.0 ± 1.9 weeks, respectively. The overall incidence of macrosomia was 6.4% (11,372/178,709), with a mean birthweight of 4,203.5 ± 232.6 g (the heaviest was 6,790 g). There were 65.5% (7,457/11,372) male and 33.9% (3,852/11,372) female infants, and the gender data of 63 macrosomic infants were missing.
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Table 1 shows the sociodemographic and clinical characteristics by birthweight category.
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Infants in the HBW and VHBW groups were more likely to be boys and of older GA than those of normal birthweight. Mothers bearing HBW and VHBW infants were more frequently
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≥ 35 years compared with those of normal birthweight infants. Larger proportions of mothers
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in the HBW and VHBW groups had high occurrences of GDM and obesity. The impacts of macrosomia on maternal outcome compared with the normal birthweight infants are presented in Table 2. Mothers who delivered infants with macrosomia were less likely to have vaginal deliveries without vacuum extraction and low forceps (HBW 38.63%,
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VHBW 26.07%) than the reference group (55.16%) but more likely to have cesarean delivery
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(HBW 59.13%, VHBW 71.79%, reference group 43.30%). ORs for cesarean delivery were 2.07 (95% CI: 1.99–2.16) for HBW and 3.31 (95% CI: 2.93–3.74) for VHBW. In vaginal deliveries, HBW infants had statistically excess risks of vacuum extraction and low forceps (both p < 0.05). Although VHBW infants were less likely to have low forceps delivery (0.58%) compared with the reference group (1.16%), there was no significant difference between these two groups. Mothers with infants with macrosomia had a higher risk of
composite obstetric complications. In particular, cephalopelvic disproportion, occurring in 2.01% in the HBW group and 7.42% in the VHBW group, was associated with macrosomia. ORs for cephalopelvic disproportion were 2.55 (95% CI: 1.25–3.91) for HBW and 9.96 (95% CI: 7.87–12.35) for VHBW. Similar associations were observed for labor extension and postpartum hemorrhage (Table 2). Table 3 shows the results for neonatal outcome characteristics. There was no difference in mortality between the HBW and reference groups, with 0.06% mortality in the HBW
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group during the first 28 days compared with 0.07% in the reference group. VHBW was
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associated with higher postnatal mortality (0.23%), which was a 3.3-fold higher risk than that in the reference group. The HBW group was 1.2-fold more likely to experience
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hospitalization. An even greater increase in risk was observed for VHBW (2.7-fold). ORs for
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HBW and VHBW infants were 1.38 (95% CI: 1.28–1.49) and 2.92 (95% CI: 2.51–3.41), respectively.
The neonatal disorders are displayed in Table 3. The leading cause of hospitalization in HBW and VHBW infants was hypoglycemia (3.59% and 6.42%, respectively). These rates
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were significantly higher than that of the reference group. HBW had a 4.4-fold increased risk
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of hypoglycemia, which was even greater in the VHBW group (5.2-fold). VHBW infants had an increased incidence of composite server neonatal disorder (48.9‰) and required more respiratory supports (including oxygen administration, CPAP and ventilation) (Table 3). Apgar score 0-3 at 5 min occurred in 0.18% of the reference group, with a significantly excess risk in the VHBW group (3.0-fold). However, there was no significant difference in risk of Apgar score ≤ 3 at 5 min compared with that of the HBW and reference groups.
VHBW was also positively associated with respiratory morbidity compared with the reference group. Incidence of aspiration pneumonia or HMD was remarkably increased in the VHBW group. The results were similar for the higher risk of neurological disorders in the VHBW group in contrast to the reference group. The VHBW group had a 3.0- and 3.5-fold excess risk of HIE and ICH, respectively.
Conclusions
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The increased risks of maternal and neonatal poor outcomes in our study are in general
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agreement with those of previous studies [1, 2, 16] and support the definition of macrosomia as ≥ 4,000 g. We also found that as birthweight increase, so too did the risks of adverse
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outcome. Of note, infants with birthweight ≥ 4,500 g had an elevated risk of Apgar score ≤ 3 at 5 min, and respiratory and neurological disorders. Meanwhile, they needed better medical
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intervention, which included CPAP and ventilation. All these data indicated that birthweight ≥ 4,500 g was associated with more serious outcomes. In our study, we found that, as birthweight increased, so too did the risk of cesarean
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section and obstetric complications (including cephalopelvic disproportion, labor extension
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and postpartum hemorrhage). The cesarean section rates in the all macrosomic categories were significantly higher than in the control group. This might have been mainly caused by cephalopelvic disproportion in our study. Meanwhile, the risks of vacuum extraction and low forceps utilization during delivery were higher in the HBW group. However, there were no significant differences of delivery interventions between the VHBW and the control groups. These results indicate that macrosomia need more delivery interventions, but there are some
reluctance to use vacuum extraction or forceps when the fetus is suspected very large. As for neonates, cephalhematoma and clavicle fracture are common complications of vaginal delivery. We found that the incidences of cephalhematoma and clavicle fracture increased with birthweight. In particular, infants weighing ≥ 4,500 g had a 61-fold increased risk of clavicle fracture. The rates of birth injuries in all groups were remarkably low in our study compared with previous researches [2, 17]. It is reported that composite birth trauma were 4.2% in infants with birthweight < 4,000 g, 10.0% in those with birthweight 4,000–
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4,999 g, and 15.1% in those with birthweight ≥ 4,500 g; while cesarean section rates were
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9.4%, 19.4% and 38.0% in above groups, respectively [17]. By comparison with our results, composite birth trauma rates were about 15 times higher but cesarean section rates were
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lower than those in all birthweight categories. These results indicate that cesarean section
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may be beneficial for reducing newborn birth trauma. It has also been demonstrated that cesarean section might prevent adverse outcomes such as shoulder dystocia and plexus injuries [18]. Cesarean section rate, which should be < 10–15%, has increased markedly in developed and developing countries [2, 3, 19]. We observed that cesarean section rate was up
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to 43.30%, 59.13% and 71.79% in control, HBW and VHBW group respectively. This result
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suggests cesarean rate is prominently high in China. A previous study also reported that the overall rate of cesarean section in mainland China was 54.90% [20]. However, for other reasons, cesarean section as a preventive measure in infants with macrosomia is controversial [21-24]. It is reported that elective cesarean section is associated with neonatal respiratory morbidity, especially when GA is < 39 weeks [25]. Thus, selecting an eligible delivery mode for infants with macrosomia may be beneficial for improving poor outcome.
There was a markedly higher risk of neonatal mortality associated with large infants whose birthweight was ≥ 4,500 g in this study. We also showed an increased risk of hospitalization in all macrosomic birthweight categories, with a 1.3-fold increase in infants weighing 4,000–4,499 g and a 2.7-fold increase for birthweight ≥ 4,500 g. Hypoglycemia is an important complication of macrosomia and represents the major cause of neonatal hospitalization [2, 26]. We found an increased risk of hypoglycemia from 3.59% in the HBW group to 6.42% in the VHBW group. However, higher incidences of hypoglycemia (5.79% in
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the 4,000–4,250 g and 6.35% in the 4,251–4,500 g group) were reported in East Asia [24]. Of
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note, maternal GDM is the prominent cause of neonatal hypoglycemia. Thus, the lower incidence of hypoglycemia could be attributed to parallel lower prevalence of maternal GDM
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in this study. We observed that the risks of composite severe disorder and mortality were
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associated with large infants. Infants with birthweight ≥ 4,500 g had a three times increased risk of low Apgar score (≤ 3) at 5 min. This result agreed with previous research showing that the rate of Apgar score ≤ 3 increased with birthweight [1]. A recent Lancet review showed that low Apgar score played a prominent role in neonatal mortality and could be attributed to
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anoxia, which is an important cause of neonatal neurological diseases [27]. In our study,
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VHBW had 2.2- and 3.5-fold increased risk of HIE and ICH, respectively, whereas neonates weighing 2,500–3,999 g and 4,000–4.499 kg both presented with low rates of Apgar score ≤ 3 and neurological disorders. In agreement with previous studies, we also observed that the VHBW group had 2.3- and 7.7-fold excess risks of aspiration pneumonia and HMD, respectively [9]. However, HMD is a neonatal complication that is strongly associated with prematurity as a consequence of immature lungs. Mothers with diabetes may bear newborn
with an inappropriate birthweight or even macrosomia, who have a high risk of HMD because of immature lung functions [28]. In our study of term births, the highest prevalence of maternal GDM was observed in the VHBW group. Therefore, the incidence of HMD among infants with large birthweight in this study population was probably attributed to GDM in the mothers. We investigated the main methods of treatments during hospitalization among all infants. We found that infants with macrosomia were more likely to need oxygen support and intravenous fluids. In particular, VHBW was associated with more requests of
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noninvasive and invasive respiratory intervention. These results suggest that birthweight of ≥
beneficial indicator of severe newborn disorder.
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4,000 g was associated with neonatal hypoglycemia and birthweight of ≥ 4,500 g could be a
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In conclusion, macrosomia is associated with greater poor maternal and neonatal outcomes and increased use of neonatology services. A definition of macrosomia as
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birthweight ≥ 4,000 g could be beneficial as an indicator of obstetric and neonatal complications, and ≥ 4,500 g may be more predictive of severe infant morbidity and mortality
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risk.
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Declaration of interest
The authors declare no conflict of interest.
References [1] Boulet S, Alexander GR, Salihu HM, Pass M. Macrosomic births in the United States: determinants,
outcomes,
and
proposed
grades
of
risk.
Am
J
ObstetGynecol
2003;188:1372-1378. [2] Koyanagi A, Zhang J, Daqvadori A, Hirayama F, Shibuya K, Souza JP, et al: Macrosomia in 23 developing countries: an analysis of a multicountry, facility-based, cross-sectional survey. Lancet 2014;381:476-483.
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[3] Li G, Kong L, Li Z, Zhang L, Fan L, Zou L, et al. Prevalence of macrosomia and its risk
infants. Paediatr Perinat Epidemiol 2014;28:345-350.
TE
factors in china: a mutlticentre survey based on birth data involving 101,723 singleton term
EP
[4] Ye J, Zhang L, Chen Y, Fang F, Luo Z, Zhang J. Searching for the definition of
AC C
macrosomia through an outcome-based approach. Plos One 2014;9:e100192. [5] Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005;115:e290-296.
for
intervention
in
gestational
diabietes
and
obesity.
ObstetGynecol
JU
targets
ST
[6] Scifres C, Feghali M, Althouse AD, Caritis S, Catov J. Adverse outcomes and potential
2015;126:316-325.
[7] Weng YH, Yang CY, Chiu YW. Risk assessment of adverse birth outcomes in relation to maternal age. Plos One 2014;9:e114843. [8]
Henriksen
T.
The
macrosomia
ActaObstetGynecolScand 2008;87:134-145.
fetus:
a
challenge
in
current
obstetrics.
[9] Voldner N, Qvigstad E, Froslie KF, Godang K, Henriksen T and Bollerslev J. Increased risk of macrosomia among overweight women with high gestational rise in fasting glucose. J Matren Fetal Neonatal Med 2010;23:74-81. [10] Zhang X, Decker A, Platt RW, Kramer MS. How big is too big? The perinatal consequences of fetal macrosomia. Am J ObstetGynecol 2008;198:517. e-1-6. [11] Engle WA, American Academy of Pediatrics Committee on Fetus and Newborn. Age terminology during the perinatal period. Pediatrics 2004;114:1362-1364.
D
[12] Weinert LS. International Association of Diabetes and Pregnancy Study Groups
TE
recommendations on the diagnosis and classification of hyperglycemia in pregnancy:
Consensus Panel. Diabetes Care 2010;33:e97.
EP
comment to the International Association of Diabetes and Pregnancy Study Groups
AC C
[13] International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA and Damm P. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676-682.
ST
[14] Zhou BF, Cooperative Meta-Analysis Group of the Working Group on Obesity in China.
JU
Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci 2002;15:83-96. [15] Tuncalp O, Souza JP, Gulmezoglu M and World Health Organization. New WHO recommendations
on
prevention
GynaecolObstet 2013;123:254-256.
and
treatment
of
postpartum
hemorrhage.Int
J
[16] Gyurkovits Z, Kallo K, Bakki J, Katona M, Bito T, Pai A and Orvos H. Neonatal outcome
of
macrosomic
infants:
an
analysis
of
a
two-year
period.
Eur
J
ObstetGynecolReprodBiol 2011;159:289-292. [17] King JR, Korst LM, Miller DA and Ouzounian JG. Increased composite maternal and neonatal morbidity associated with ultrasonographically suspected fetal macrosomia. J Matern Fetal Neonatal Med 2012;25:1953-1959. [18] Hankins GD, Clark SM and Munn MB. Cesarean section on request at 39 weeks: inpact
D
on shoulder dystocia, fetal trauma, neonatal encephalopathy and intrauterine fetal demise.
TE
SeminPerinatol 2006;30:276-287.
[19] Bjortad AR, Irqens-Hansen K, Daltveit AK and Irgens LM. Macrosomia: mode of
EP
delivery and pregnancy outcome. ActaObstetGynecolScand 2010;89:664-669.
AC C
[20] Liu Y, Li G, Chen Y, Wang X, Ruan Y, Zou L, et al. A descriptive analysis of the indications for caesarean section in mainland China. BMC Pregnancy Childbirth 2014;14:410.
[21] Ye J, Betran AP, Guerrero Vela M, Souza JP and Zhang J. Searching for the optimal rate
ST
of medically necessary cesarean delivery. Birth 2014;41:237-244.
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[22] Ecker J. Elective cesarean delivery on maternal request. JAMA 2013;309:1930-1936. [23] Lee YM and Dalton ME. Cesarean delivery on maternal request: maternal and neonatal complications. CurrOpinObstetGynecol 2008;20:597-601. [24] Weissmann-Brenner A, Simchen MJ, Ziberberg E, Kalter A, Weisz B and Achiron R. Maternal
and
neonatal
outcomes
of
ActaObstetGynecolScand 2012;91:844-849.
large
for
gestational
age
pregnancies.
[25] Chiossi G, Lai Y, Landon MB, Spong CY, Rouse DJ, Varner MW et al. Timing of delivery and adverse outcomes in term singleton repeat cesarean deliveries. ObstetGynecol 2013;121:561-569. [26] Cordero L, Paetow P, Landon MB and Nankervis CA. Neonatal outcomes of macrosomic infants of diabetic and non-diabetic mothers. 2015, J Neonatal Perinatal Med 2015;8:105-112. [27] Iliodromiti S, Mackay DF, Smith GC, Pell JP and Nelson SM. Apgar score and the risk cause-specific
infant
mortality:
a
population-based
cohort
study.
Lancet
D
of
TE
2014;384:1749-1755.
[28] Lock M, McGillick EV, Orgeig, S, McMilen IC and Morrisson JL. Regulation of fetal
EP
lung development in response to maternal overnutrition.Clin Exp Pharmacol Physiol
JU
ST
AC C
2013;40:803-816.
Tables Table 1 Sociodemographic and clinical characteristics by birthweight 4,000–4,499 g
≥ 4,500 g
(n = 142,615)
(n = 10,064)
(n = 1,308)
Birthweight (mean±SD)
3,322.9 ± 334.7
4,139.1 ± 129.6
4,701.1 ± 252.0
GA at delivery (mean±SD)
39.5 ± 1.0
39.9 ± 1.1
40.4 ± 1.2
GA ≥ 40 weeks % ( n)
36.1 (51,515)
54.5 (5,493)
55.9 (731)
Male infant % ( n)
51.7 (73,799)
64.3 (6,549)
69.4 (908)
Multiparity % ( n)
26.4 (37,579)
33.6 (3,379)
Maternal age ≥ 35 years % ( n)
8.6 (12,251)
13.7 (1,130)
16.0 (209)
GDM % ( n)
2.7 (3,790)
6.2 (622)
11.2 (147)
Obesity % ( n)
0.1 (122)
0.3 (30)
1.0 (13)
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2,500–3,999 g
37.5 (490)
All sociodemographic and clinical characteristics differed significantly (p < 0.01) by
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birthweight categories.
Table 2 Maternal outcomes by birthweight Maternal outcomes
Cesarean delivery % ( n) OR (95% CI)
2,500–3,999 g
4,000–4,499 g
≥ 4,500 g
(n = 142,615)
(n = 10,064)
(n = 1,308)
43.30 (61,745)
59.13 (5,951) ★★
71.79 (939) ▲▲
1.00
2.07 (1.99–2.16) 3.31
p value
0.000
(2.93–
3.74） 0.000
0.16 (130)
OR (95% CI)
1.00
OR (95% CI)
1.00
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p value
1.16 (937)
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Low forceps % ( n)
0.58 (2)
1.89 (1.16–3.49) 3.67 0.032
15.01)
1.56 (62) ★
0.058
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p value
0.30 (12) ★
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Vacuum extraction % ( n)
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Any intervention
(0.97–
1.45 (1.13–1.87) 0.58 (2) 0.022
0.51 (0.14–1.91) 0.315
Any obstetric complication
( n)
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Cephalopelvic disproportion % 0.76 (1089) 1.00
OR (95% CI) p value
Labor extension % ( n) OR (95% CI)
2.01 (202) ★★
7.42 (97) ▲▲
2.55 (1.25–3.91) 9.96
(7.87–
0.000
12.35)
0.47 (672)
1.60 (161) ★★
0.000
1.00
3.42 (1.97–5.93) 3.06 (40) ▲▲ 0.000
6.84
(4.48–
p value Postpartum hemorrhage % ( n)
0.25 (358)
0.60 (60) ★
1.00
3.79 (2.16–6.72) 0.000
OR (95% CI)
10.21)
1.61 (21) ▲▲
0.044
p value
9.46
(6.55–
17.01) 0.005 OR: odds ratio; CI: confidence interval. OR estimated from logistic regression models
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adjusted for gestational age and infant sex.
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4,000-4,499 g vs. 2,500-3,999 g: ★p < 0.05, ★★ p < 0.01; ≥ 4,500 g vs. 2,500-3,999 g: ▲ p
Predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes Dan Wang, Li Zhu, Shulian Zhang, Xueqin Wu, Xiaoli Wang, Qin Lv, Dongmei Gan, Ling Liu, Wen Li, Qin Zhou, Jiarong Lu, Haiying He, Jimei Wang, Hua Xin, Zhankui Li, Chao Chen Doi: 10.3109/14767058.2016.1147549 Abstract OBJECTIVE: We examined the predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes. STUDY DESIGN: This was a multicenter, retrospective cohort study conducted in China. We selected 178,709 singletons weighing ≥ 2,500 g with gestational age 37– 44 weeks. We categorized macrosomia with two gradations (4,000–4,499 g and ≥ 4,500 g) and compared them with a normosomic reference group of infants with birthweight 2,500–3,999 g. RESULTS: The risks of obstetric and neonatal complications increased when infants had a birthweight of ≥ 4,000 g. The rates of infant mortality, Apgar score ≤ 3 at 5 min, respiratory and neurological disorders rose significantly among neonates weighing ≥ 4,500 g. CONCLUSION: A definition of macrosomia as birthweight ≥ 4,000 g could be beneficial as an indicator of obstetric and newborn complications, and birthweight ≥ 4,500 g might be predictive of severe infant morbidity and mortality risk.
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Predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes Dan Wang1, Li Zhu1, Shulian Zhang1, Xueqin Wu2, Xiaoli Wang3, Qin Lv4, Dongmei Gan4, Ling Liu5, Wen Li6, Qin Zhou7, Jiarong Lu8, Haiying He9, Jimei Wang10, Hua Xin11, Zhankui Li12, Chao Chen1* 1
Department of Neonatology, Children’s Hospital of Fudan University, Shanghai, China.
2
Zhejiang Jiaxing The First Hospital, China. 3Shanghai Jiading Maternal and Child Care
Hospital, China. 4Ningbo Women and Children’s Hospital, China. 5Guizhou Maternal and Child Care Hospital, China. 6Qilu Hospital of Shangdong University, China. 7Jiangsu Wuxi
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Maternal and Child Health Care Hospital, China. 8Xinjiang Yili Maternal and Child Care
Gynecology Hospital of Fudan University, China. 12
Obstetrics and
Xinjiang Boertala Hospital, China.
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Shanxi Maternal and Child Care Hospital, China.
11
10
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Hospital, China. 9The Third Hospital of Baotou Steel Group, China.
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* Correspondence to: Chao Chen, No. 399 Wanyuan Road, Shanghai 201102, PR China. E-mail addresses: [email protected] (Chao Chen).
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Tel: 8621-64931990
Abstract OBJECTIVE: We examined the predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes. STUDY DESIGN: This was a multicenter, retrospective cohort study conducted in China. We selected 178,709 singletons weighing ≥ 2,500 g with gestational age 37–44 weeks. We categorized macrosomia with two gradations (4,000–4,499 g and ≥ 4,500 g) and compared them with a normosomic reference group of infants with birthweight 2,500–3,999 g.
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RESULTS: The risks of obstetric and neonatal complications increased when infants had a
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birthweight of ≥ 4,000 g. The rates of infant mortality, Apgar score ≤ 3 at 5 min, respiratory and neurological disorders rose significantly among neonates weighing ≥ 4,500 g.
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CONCLUSION: A definition of macrosomia as birthweight ≥ 4,000 g could be beneficial as
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an indicator of obstetric and newborn complications, and birthweight ≥ 4,500 g might be predictive of severe infant morbidity and mortality risk.
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Keywords: Macrosomia, birthweight, threshold, outcome
Introduction The term “macrosomia” is used to describe an abnormally large fetus or neonate. No consensus has been reached to define macrosomia [1-4]. Macrosomia is variously characterized by birthweight of ≥ 4,000 g, ≥ 4,500 g and ≥ 5,000 g, and is associated with numerous maternal and neonatal complications. For mothers, bearing macrosomia increases risks of cesarean section, prolonged labor, postpartum hemorrhage and third- and fourth-degree lacerations [2]. For neonates, macrosomia is associated with birth trauma,
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perinatal asphyxia, shoulder dystocia and death [4]. Children who have macrosomia at birth
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and were exposed to an intrauterine environment of diabetes or maternal obesity are at an increased risk of developing metabolic syndrome [5]. Therefore, macrosomia has become a
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frequent challenge.
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In recent decades, worldwide, there have been increases in mean birthweight, mean birthweight for gestational age, and the prevalence of large-for-gestational-age (LGA; weight > 90th percentile for gestational age) [1, 2]. In China, investigators also showed an increase in prevalence of macrosomia from 6.0% in 1994, to 7.3% in 2014 [3]. Risk factors that increase
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the possibility of bearing an infant with macrosomia include advanced maternal age, maternal
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height, multiparity, previous macrosomia, maternal obesity, gestational diabetes mellitus (GDM) and male fetus [1-6]. Given that pregnant women are now older, heavier and more likely to have diabetes mellitus than before, this may lead to larger babies [8, 9]. The aim of this study, which used recent multicenter birth data in China, was to determine predictive thresholds for adverse maternal or neonatal outcomes, including maternal complications, neonatal morbidity and infant mortality. Although it is widely
accepted that large birthweight is associated with excess risk of neonatal death, the birthweight cutoffs that signal significant increases in general maternal or neonatal poor outcomes have yet to be determined.
Methods and materials Data We extracted data from the Chinese Neonatal Network, which contains birth records in China,
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covering seven representative geographic areas: North (Hebei, Shanxi and Shandong
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Provinces and Inner Mongolia Autonomous Region); Northeast (Heilongjiang and Liaoning Provinces); East (Jiangsu, Zhejiang and Anhui Provinces and Shanghai city); Central (Henan
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and Hubei Provinces); Southern (Guangdong and Fujian Provinces and Guangxi Autonomous
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Region); Southwest (Sichuan, Guizhou and Yunnan Provinces and Tibet Autonomous Region); and Northwest (Shanxi and Gansu Provinces, and Ningxia and Xinjiang Autonomous Regions). Primary-level hospitals that did not provide obstetric services were excluded from this study. This study was conducted in 23 provinces or autonomous regions
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infants.
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in China from May 2010 to April 2014. A total of 58 hospitals were recruited, with 178,709
Data collection We obtained data from medical records in each participating hospital. All investigators were trained and accredited prior to this survey. Each completed questionnaire was checked by a field supervisor at the provincial level. Data were registered in a specially designed network database by two physicians or midwives independently with automated monitor for
out-of-range values and logic mistakes. The research ethics boards of each participant hospital approved the protocol. Definition Macrosomia was defined as a birthweight of ≥ 4,000 g, regardless of gestational age (GA) [2, 8]. Previous studies suggested that there was a significant difference in adverse birth outcomes between birthweights of 2,500–3,999 g and ≥ 4,000 g [2, 8]. Therefore, we used a birthweight of 2,500–3,999 g and GA of 37–42 weeks as a reference group (142,615 infants
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[79.8%]). Moreover, given that macrosomic infants with birthweight ≥ 4,500 g have an
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increased risk of still birth compared to those with birthweight 4.0–4.49 kg [10], we divided macrosomia into high birthweight group (HBW; birthweight of 4,000–4,499 g, irrespective of
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GA; 10,064 infants [5.6%]) and very high birthweight group (VHBW; birthweight of ≥ 4,500
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g, irrespective of GA; 1,308 infants [0.7%]). The remaining group contained infants with birthweight < 2,500 g, comprising 24,722 births (13.8%). In our analysis of all births, marcosomia risk factors in the correlation data included maternal age, GA at delivery, parity, GDM, obesity, and gender of newborn. Maternal age
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was defined as completed years at time of delivery and classified into two categories: < 35
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years and ≥ 35 years. GA was the time elapsed between the first day of the last normal menstrual period and the day of delivery. If pregnancy was achieved using assisted reproductive technology, GA was calculated by adding two weeks to the age of conception [11]. GA was separated into ≤ 40 and > 40 weeks. Parity was defined as the number of live births before the index pregnancy and divided into primiparity and multiparity. GDM criteria were suggested by the International Association of Diabetes and Pregnancy Study Group [12,
13]. Maternal obesity was characterized by body mass index ≥ 30 kg/m2 [14]. The main maternal characteristics were mode of delivery (including vaginal and cesarean delivery), intervention during delivery (including vacuum extraction and low forceps) and obstetric complications (including cephalopelvic disproportion, labor extension and postpartum hemorrhage). Postpartum hemorrhage was defined as a blood loss of ≥ 500 ml within 24 h after birth, according to the recommendation of the World Health Organization [15]. We defined composite obstetric complication as cephalopelvic
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disproportion, labor extension and postpartum hemorrhage.
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The primary neonatal outcome measures were mortality and hospitalization. Neonatal mortality was assessed by deaths happening in the first 28 days after birth. Neonatal
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hospitalization was the administration to the common neonatal ward or neonatal intensive care
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unit. The secondary outcome measures included Apgar score ≤ 3 at 5 min, birth trauma, hypoglycemia and respiratory and neurological disorders. Hypoglycemia was characterized as blood glucose < 2.6 mmol/L at any time point during the stay in-hospital, irrespective of GA or hour of life. Cephalohematoma and clavicle fracture were classified as birth trauma. Hypoxic
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ischemic encephalopathy (HIE) and intracranial hemorrhage (ICH) were categorized as
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neurological morbidity. We also defined respiratory morbidity as any form of respiratory distress (including aspiration pneumonia and hyaline membrane disease [HMD]) that necessitated admission of the neonate to the common neonatal ward or intensive care unit irrespective of the need for any diagnostic tests or therapeutic intervention. In contrast, respiratory support included the entire spectrum ranging from nasal cannula and neonatal continuous positive airway pressure (CPAP) to mechanical ventilation. Indications for
intravenous fluids included any primary gastrointestinal pathological condition or a nutrition-related disorder, such as feeding intolerance or hypoglycemia. Neonates who needed intravenous fluids for their respiratory or neurological status were also included. Infants with an Apgar score ≤ 3 at 5 min, respiratory and neurological disorders need more medical attentions, therefore, we described these complications as composite severe neonatal disorder. The diagnoses of the above diseases were based on the previous criteria used in China until 2009.
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Statistical analysis
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Statistical analysis was performed with SPSS version 19. Differences in the study parameters between infants with normal birthweight and macrosomia were detected using the χ2 test for
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categorical variables and Student’s t-test for continuous variables. Logistic regression models
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were used to examine the effects of birthweight on maternal and neonatal complications, controlling for maternal age, GA at delivery, delivery mode, infant gender and presence of GDM. We also conducted similar logistic regression models to assess risk factors for macrosomia. For logistic regression models, odds ratios (OR) and 95% confidence intervals
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(95% CI) are expressed. p < 0.05 was the criterion for significance.
Results A total 178,709 singleton deliveries were recorded in 23 provinces in China from May 2010 to April 2014, with a mean birthweight and GA of 3,235 ± 533,6 g and 39.0 ± 1.9 weeks, respectively. The overall incidence of macrosomia was 6.4% (11,372/178,709), with a mean birthweight of 4,203.5 ± 232.6 g (the heaviest was 6,790 g). There were 65.5% (7,457/11,372) male and 33.9% (3,852/11,372) female infants, and the gender data of 63 macrosomic infants were missing.
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Table 1 shows the sociodemographic and clinical characteristics by birthweight category.
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Infants in the HBW and VHBW groups were more likely to be boys and of older GA than those of normal birthweight. Mothers bearing HBW and VHBW infants were more frequently
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≥ 35 years compared with those of normal birthweight infants. Larger proportions of mothers
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in the HBW and VHBW groups had high occurrences of GDM and obesity. The impacts of macrosomia on maternal outcome compared with the normal birthweight infants are presented in Table 2. Mothers who delivered infants with macrosomia were less likely to have vaginal deliveries without vacuum extraction and low forceps (HBW 38.63%,
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VHBW 26.07%) than the reference group (55.16%) but more likely to have cesarean delivery
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(HBW 59.13%, VHBW 71.79%, reference group 43.30%). ORs for cesarean delivery were 2.07 (95% CI: 1.99–2.16) for HBW and 3.31 (95% CI: 2.93–3.74) for VHBW. In vaginal deliveries, HBW infants had statistically excess risks of vacuum extraction and low forceps (both p < 0.05). Although VHBW infants were less likely to have low forceps delivery (0.58%) compared with the reference group (1.16%), there was no significant difference between these two groups. Mothers with infants with macrosomia had a higher risk of
composite obstetric complications. In particular, cephalopelvic disproportion, occurring in 2.01% in the HBW group and 7.42% in the VHBW group, was associated with macrosomia. ORs for cephalopelvic disproportion were 2.55 (95% CI: 1.25–3.91) for HBW and 9.96 (95% CI: 7.87–12.35) for VHBW. Similar associations were observed for labor extension and postpartum hemorrhage (Table 2). Table 3 shows the results for neonatal outcome characteristics. There was no difference in mortality between the HBW and reference groups, with 0.06% mortality in the HBW
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group during the first 28 days compared with 0.07% in the reference group. VHBW was
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associated with higher postnatal mortality (0.23%), which was a 3.3-fold higher risk than that in the reference group. The HBW group was 1.2-fold more likely to experience
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hospitalization. An even greater increase in risk was observed for VHBW (2.7-fold). ORs for
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HBW and VHBW infants were 1.38 (95% CI: 1.28–1.49) and 2.92 (95% CI: 2.51–3.41), respectively.
The neonatal disorders are displayed in Table 3. The leading cause of hospitalization in HBW and VHBW infants was hypoglycemia (3.59% and 6.42%, respectively). These rates
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were significantly higher than that of the reference group. HBW had a 4.4-fold increased risk
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of hypoglycemia, which was even greater in the VHBW group (5.2-fold). VHBW infants had an increased incidence of composite server neonatal disorder (48.9‰) and required more respiratory supports (including oxygen administration, CPAP and ventilation) (Table 3). Apgar score 0-3 at 5 min occurred in 0.18% of the reference group, with a significantly excess risk in the VHBW group (3.0-fold). However, there was no significant difference in risk of Apgar score ≤ 3 at 5 min compared with that of the HBW and reference groups.
VHBW was also positively associated with respiratory morbidity compared with the reference group. Incidence of aspiration pneumonia or HMD was remarkably increased in the VHBW group. The results were similar for the higher risk of neurological disorders in the VHBW group in contrast to the reference group. The VHBW group had a 3.0- and 3.5-fold excess risk of HIE and ICH, respectively.
Conclusions
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The increased risks of maternal and neonatal poor outcomes in our study are in general
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agreement with those of previous studies [1, 2, 16] and support the definition of macrosomia as ≥ 4,000 g. We also found that as birthweight increase, so too did the risks of adverse
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outcome. Of note, infants with birthweight ≥ 4,500 g had an elevated risk of Apgar score ≤ 3 at 5 min, and respiratory and neurological disorders. Meanwhile, they needed better medical
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intervention, which included CPAP and ventilation. All these data indicated that birthweight ≥ 4,500 g was associated with more serious outcomes. In our study, we found that, as birthweight increased, so too did the risk of cesarean
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section and obstetric complications (including cephalopelvic disproportion, labor extension
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and postpartum hemorrhage). The cesarean section rates in the all macrosomic categories were significantly higher than in the control group. This might have been mainly caused by cephalopelvic disproportion in our study. Meanwhile, the risks of vacuum extraction and low forceps utilization during delivery were higher in the HBW group. However, there were no significant differences of delivery interventions between the VHBW and the control groups. These results indicate that macrosomia need more delivery interventions, but there are some
reluctance to use vacuum extraction or forceps when the fetus is suspected very large. As for neonates, cephalhematoma and clavicle fracture are common complications of vaginal delivery. We found that the incidences of cephalhematoma and clavicle fracture increased with birthweight. In particular, infants weighing ≥ 4,500 g had a 61-fold increased risk of clavicle fracture. The rates of birth injuries in all groups were remarkably low in our study compared with previous researches [2, 17]. It is reported that composite birth trauma were 4.2% in infants with birthweight < 4,000 g, 10.0% in those with birthweight 4,000–
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4,999 g, and 15.1% in those with birthweight ≥ 4,500 g; while cesarean section rates were
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9.4%, 19.4% and 38.0% in above groups, respectively [17]. By comparison with our results, composite birth trauma rates were about 15 times higher but cesarean section rates were
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lower than those in all birthweight categories. These results indicate that cesarean section
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may be beneficial for reducing newborn birth trauma. It has also been demonstrated that cesarean section might prevent adverse outcomes such as shoulder dystocia and plexus injuries [18]. Cesarean section rate, which should be < 10–15%, has increased markedly in developed and developing countries [2, 3, 19]. We observed that cesarean section rate was up
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to 43.30%, 59.13% and 71.79% in control, HBW and VHBW group respectively. This result
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suggests cesarean rate is prominently high in China. A previous study also reported that the overall rate of cesarean section in mainland China was 54.90% [20]. However, for other reasons, cesarean section as a preventive measure in infants with macrosomia is controversial [21-24]. It is reported that elective cesarean section is associated with neonatal respiratory morbidity, especially when GA is < 39 weeks [25]. Thus, selecting an eligible delivery mode for infants with macrosomia may be beneficial for improving poor outcome.
There was a markedly higher risk of neonatal mortality associated with large infants whose birthweight was ≥ 4,500 g in this study. We also showed an increased risk of hospitalization in all macrosomic birthweight categories, with a 1.3-fold increase in infants weighing 4,000–4,499 g and a 2.7-fold increase for birthweight ≥ 4,500 g. Hypoglycemia is an important complication of macrosomia and represents the major cause of neonatal hospitalization [2, 26]. We found an increased risk of hypoglycemia from 3.59% in the HBW group to 6.42% in the VHBW group. However, higher incidences of hypoglycemia (5.79% in
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the 4,000–4,250 g and 6.35% in the 4,251–4,500 g group) were reported in East Asia [24]. Of
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note, maternal GDM is the prominent cause of neonatal hypoglycemia. Thus, the lower incidence of hypoglycemia could be attributed to parallel lower prevalence of maternal GDM
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in this study. We observed that the risks of composite severe disorder and mortality were
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associated with large infants. Infants with birthweight ≥ 4,500 g had a three times increased risk of low Apgar score (≤ 3) at 5 min. This result agreed with previous research showing that the rate of Apgar score ≤ 3 increased with birthweight [1]. A recent Lancet review showed that low Apgar score played a prominent role in neonatal mortality and could be attributed to
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anoxia, which is an important cause of neonatal neurological diseases [27]. In our study,
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VHBW had 2.2- and 3.5-fold increased risk of HIE and ICH, respectively, whereas neonates weighing 2,500–3,999 g and 4,000–4.499 kg both presented with low rates of Apgar score ≤ 3 and neurological disorders. In agreement with previous studies, we also observed that the VHBW group had 2.3- and 7.7-fold excess risks of aspiration pneumonia and HMD, respectively [9]. However, HMD is a neonatal complication that is strongly associated with prematurity as a consequence of immature lungs. Mothers with diabetes may bear newborn
with an inappropriate birthweight or even macrosomia, who have a high risk of HMD because of immature lung functions [28]. In our study of term births, the highest prevalence of maternal GDM was observed in the VHBW group. Therefore, the incidence of HMD among infants with large birthweight in this study population was probably attributed to GDM in the mothers. We investigated the main methods of treatments during hospitalization among all infants. We found that infants with macrosomia were more likely to need oxygen support and intravenous fluids. In particular, VHBW was associated with more requests of
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noninvasive and invasive respiratory intervention. These results suggest that birthweight of ≥
beneficial indicator of severe newborn disorder.
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4,000 g was associated with neonatal hypoglycemia and birthweight of ≥ 4,500 g could be a
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In conclusion, macrosomia is associated with greater poor maternal and neonatal outcomes and increased use of neonatology services. A definition of macrosomia as
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birthweight ≥ 4,000 g could be beneficial as an indicator of obstetric and neonatal complications, and ≥ 4,500 g may be more predictive of severe infant morbidity and mortality
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risk.
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Declaration of interest
The authors declare no conflict of interest.
References [1] Boulet S, Alexander GR, Salihu HM, Pass M. Macrosomic births in the United States: determinants,
outcomes,
and
proposed
grades
of
risk.
Am
J
ObstetGynecol
2003;188:1372-1378. [2] Koyanagi A, Zhang J, Daqvadori A, Hirayama F, Shibuya K, Souza JP, et al: Macrosomia in 23 developing countries: an analysis of a multicountry, facility-based, cross-sectional survey. Lancet 2014;381:476-483.
D
[3] Li G, Kong L, Li Z, Zhang L, Fan L, Zou L, et al. Prevalence of macrosomia and its risk
infants. Paediatr Perinat Epidemiol 2014;28:345-350.
TE
factors in china: a mutlticentre survey based on birth data involving 101,723 singleton term
EP
[4] Ye J, Zhang L, Chen Y, Fang F, Luo Z, Zhang J. Searching for the definition of
AC C
macrosomia through an outcome-based approach. Plos One 2014;9:e100192. [5] Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005;115:e290-296.
for
intervention
in
gestational
diabietes
and
obesity.
ObstetGynecol
JU
targets
ST
[6] Scifres C, Feghali M, Althouse AD, Caritis S, Catov J. Adverse outcomes and potential
2015;126:316-325.
[7] Weng YH, Yang CY, Chiu YW. Risk assessment of adverse birth outcomes in relation to maternal age. Plos One 2014;9:e114843. [8]
Henriksen
T.
The
macrosomia
ActaObstetGynecolScand 2008;87:134-145.
fetus:
a
challenge
in
current
obstetrics.
[9] Voldner N, Qvigstad E, Froslie KF, Godang K, Henriksen T and Bollerslev J. Increased risk of macrosomia among overweight women with high gestational rise in fasting glucose. J Matren Fetal Neonatal Med 2010;23:74-81. [10] Zhang X, Decker A, Platt RW, Kramer MS. How big is too big? The perinatal consequences of fetal macrosomia. Am J ObstetGynecol 2008;198:517. e-1-6. [11] Engle WA, American Academy of Pediatrics Committee on Fetus and Newborn. Age terminology during the perinatal period. Pediatrics 2004;114:1362-1364.
D
[12] Weinert LS. International Association of Diabetes and Pregnancy Study Groups
TE
recommendations on the diagnosis and classification of hyperglycemia in pregnancy:
Consensus Panel. Diabetes Care 2010;33:e97.
EP
comment to the International Association of Diabetes and Pregnancy Study Groups
AC C
[13] International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA and Damm P. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676-682.
ST
[14] Zhou BF, Cooperative Meta-Analysis Group of the Working Group on Obesity in China.
JU
Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci 2002;15:83-96. [15] Tuncalp O, Souza JP, Gulmezoglu M and World Health Organization. New WHO recommendations
on
prevention
GynaecolObstet 2013;123:254-256.
and
treatment
of
postpartum
hemorrhage.Int
J
[16] Gyurkovits Z, Kallo K, Bakki J, Katona M, Bito T, Pai A and Orvos H. Neonatal outcome
of
macrosomic
infants:
an
analysis
of
a
two-year
period.
Eur
J
ObstetGynecolReprodBiol 2011;159:289-292. [17] King JR, Korst LM, Miller DA and Ouzounian JG. Increased composite maternal and neonatal morbidity associated with ultrasonographically suspected fetal macrosomia. J Matern Fetal Neonatal Med 2012;25:1953-1959. [18] Hankins GD, Clark SM and Munn MB. Cesarean section on request at 39 weeks: inpact
D
on shoulder dystocia, fetal trauma, neonatal encephalopathy and intrauterine fetal demise.
TE
SeminPerinatol 2006;30:276-287.
[19] Bjortad AR, Irqens-Hansen K, Daltveit AK and Irgens LM. Macrosomia: mode of
EP
delivery and pregnancy outcome. ActaObstetGynecolScand 2010;89:664-669.
AC C
[20] Liu Y, Li G, Chen Y, Wang X, Ruan Y, Zou L, et al. A descriptive analysis of the indications for caesarean section in mainland China. BMC Pregnancy Childbirth 2014;14:410.
[21] Ye J, Betran AP, Guerrero Vela M, Souza JP and Zhang J. Searching for the optimal rate
ST
of medically necessary cesarean delivery. Birth 2014;41:237-244.
JU
[22] Ecker J. Elective cesarean delivery on maternal request. JAMA 2013;309:1930-1936. [23] Lee YM and Dalton ME. Cesarean delivery on maternal request: maternal and neonatal complications. CurrOpinObstetGynecol 2008;20:597-601. [24] Weissmann-Brenner A, Simchen MJ, Ziberberg E, Kalter A, Weisz B and Achiron R. Maternal
and
neonatal
outcomes
of
ActaObstetGynecolScand 2012;91:844-849.
large
for
gestational
age
pregnancies.
[25] Chiossi G, Lai Y, Landon MB, Spong CY, Rouse DJ, Varner MW et al. Timing of delivery and adverse outcomes in term singleton repeat cesarean deliveries. ObstetGynecol 2013;121:561-569. [26] Cordero L, Paetow P, Landon MB and Nankervis CA. Neonatal outcomes of macrosomic infants of diabetic and non-diabetic mothers. 2015, J Neonatal Perinatal Med 2015;8:105-112. [27] Iliodromiti S, Mackay DF, Smith GC, Pell JP and Nelson SM. Apgar score and the risk cause-specific
infant
mortality:
a
population-based
cohort
study.
Lancet
D
of
TE
2014;384:1749-1755.
[28] Lock M, McGillick EV, Orgeig, S, McMilen IC and Morrisson JL. Regulation of fetal
EP
lung development in response to maternal overnutrition.Clin Exp Pharmacol Physiol
JU
ST
AC C
2013;40:803-816.
Tables Table 1 Sociodemographic and clinical characteristics by birthweight 4,000–4,499 g
≥ 4,500 g
(n = 142,615)
(n = 10,064)
(n = 1,308)
Birthweight (mean±SD)
3,322.9 ± 334.7
4,139.1 ± 129.6
4,701.1 ± 252.0
GA at delivery (mean±SD)
39.5 ± 1.0
39.9 ± 1.1
40.4 ± 1.2
GA ≥ 40 weeks % ( n)
36.1 (51,515)
54.5 (5,493)
55.9 (731)
Male infant % ( n)
51.7 (73,799)
64.3 (6,549)
69.4 (908)
Multiparity % ( n)
26.4 (37,579)
33.6 (3,379)
Maternal age ≥ 35 years % ( n)
8.6 (12,251)
13.7 (1,130)
16.0 (209)
GDM % ( n)
2.7 (3,790)
6.2 (622)
11.2 (147)
Obesity % ( n)
0.1 (122)
0.3 (30)
1.0 (13)
AC C
EP
TE
D
2,500–3,999 g
37.5 (490)
All sociodemographic and clinical characteristics differed significantly (p < 0.01) by
JU
ST
birthweight categories.
Table 2 Maternal outcomes by birthweight Maternal outcomes
Cesarean delivery % ( n) OR (95% CI)
2,500–3,999 g
4,000–4,499 g
≥ 4,500 g
(n = 142,615)
(n = 10,064)
(n = 1,308)
43.30 (61,745)
59.13 (5,951) ★★
71.79 (939) ▲▲
1.00
2.07 (1.99–2.16) 3.31
p value
0.000
(2.93–
3.74） 0.000
0.16 (130)
OR (95% CI)
1.00
OR (95% CI)
1.00
ST
p value
1.16 (937)
AC C
Low forceps % ( n)
0.58 (2)
1.89 (1.16–3.49) 3.67 0.032
15.01)
1.56 (62) ★
0.058
EP
p value
0.30 (12) ★
TE
Vacuum extraction % ( n)
D
Any intervention
(0.97–
1.45 (1.13–1.87) 0.58 (2) 0.022
0.51 (0.14–1.91) 0.315
Any obstetric complication
( n)
JU
Cephalopelvic disproportion % 0.76 (1089) 1.00
OR (95% CI) p value
Labor extension % ( n) OR (95% CI)
2.01 (202) ★★
7.42 (97) ▲▲
2.55 (1.25–3.91) 9.96
(7.87–
0.000
12.35)
0.47 (672)
1.60 (161) ★★
0.000
1.00
3.42 (1.97–5.93) 3.06 (40) ▲▲ 0.000
6.84
(4.48–
p value Postpartum hemorrhage % ( n)
0.25 (358)
0.60 (60) ★
1.00
3.79 (2.16–6.72) 0.000
OR (95% CI)
10.21)
1.61 (21) ▲▲
0.044
p value
9.46
(6.55–
17.01) 0.005 OR: odds ratio; CI: confidence interval. OR estimated from logistic regression models
D
adjusted for gestational age and infant sex.
TE
4,000-4,499 g vs. 2,500-3,999 g: ★p < 0.05, ★★ p < 0.01; ≥ 4,500 g vs. 2,500-3,999 g: ▲ p
