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Pregnancy and neonatal outcome after bariatric surgery
Best Practice & Research Clinical Obstetrics and Gynaecology 29 (2015) 133e144
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13
Pregnancy and neonatal outcome after bariatric surgery Kent Willis, MD a, *, Nicky Lieberman, MD b, Eyal Sheiner, MD, PhD, Deputy Director General, Professor and Senior Researcher c a
Our Lady of the Lake Regional Medical Center, Baton Rouge, LA, USA Head of Community Medicine Department, Clalit Health Services Ltd., Tel Aviv, Israel c Soroka University Medical Center, Ben-Gurion University of the Negev, PO Box 151, Beer Sheva, Israel b
Keywords: bariatric surgery maternal obesity pregnancy neonatal outcome perinatal outcome pregnancy outcome
The global obesity epidemic is changing the face of maternalefetal medicine. One in five women is obese at time of conception, and increasing numbers of parturients have undergone bariatric surgery. Recent publication of large, population-based studies and comparison studies of preoperative and post-operative pregnancies have highlighted new risks and benefits to the mother and child. Pregnancy after bariatric surgery appears to effectively reduce the risk of complications such as fetal macrosomia, gestational diabetes mellitus, and hypertensive disorders of pregnancy; however, women who become pregnant after bariatric surgery may constitute a unique obstetric population with an increased risk for preterm and small-for-gestational-age infants. In this article, we provide an overview of the current knowledge of the impact of maternal bariatric surgery on neonatal and pregnancy outcomes. © 2014 Elsevier Ltd. All rights reserved.
Introduction Rising rates of obesity have created a worldwide epidemic [1]. As obesity rates in pregnant women rise, the importance of obesity-related complications also increases. Pregravid obesity has been shown
* Corresponding author. Our Lady of the Lake Children's Hospital, 5000 Hennessy Boulevard, Suite 6001, Baton Rouge, LA 70808, USA. Tel.: þ1 2254219570. E-mail addresses: [email protected] (K. Willis), [email protected] (E. Sheiner).
http://dx.doi.org/10.1016/j.bpobgyn.2014.04.015 1521-6934/© 2014 Elsevier Ltd. All rights reserved.
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to triple the risk of infertility and increase rates of miscarriage, gestational diabetes mellitus (GDM), gestational hypertension, pre-eclampsia and caesarean delivery (CD) [2e8]. Women of reproductive age are turning to bariatric surgery in increasing numbers. Currently, women aged 18-45 years undergo >50,000 inpatient bariatric surgical procedures a year in the United States [9], accounting for approximately half of all bariatric procedures [10]. This has created a new obstetric population with unique outcomes and risks for mother and child. Recent publication of large, population-based trials [11e13] and studies comparing preoperative and post-operative pregnancies [14,15] have highlighted new risks and benefits of pregnancy after surgery and confirmed prior research in this new and important field of maternalefetal and neonatal medicine. Bariatric procedures Three main classes of bariatric surgeries have been developed to date. These include restrictive, malabsorptive and combined restrictiveemalabsorptive procedures. Restrictive procedures, such as sleeve gastrectomy, vertical banded gastroplasty (VBG) and adjustable gastric banding (ABG), promote weight loss by physically decreasing gastric volume and thereby total food intake. They are generally considered safer and less complicated to perform, but they do have the disadvantage that sugary, high-energy foods may bypass the restriction. Malabsorptive procedures, such as biliopancreatic diversion (BPD), cause weight loss primarily by bypassing a significant portion of the small bowel and inducing malabsorption. Most purely malabsorptive procedures have been linked to significant safety concerns and are now rarely performed [16,17]. In the United States, most procedures are currently of the combined type, with the Roux-en-Y gastric bypass (RYGB) accounting for 93% of all procedures performed in 2000 [17]. Despite its classification, malabsorption is actually not significant in RYGB [18]. Instead, neuroendocrine changes are increasingly recognized as an important component of the weight loss effect [16]. A recent 10-year follow-up of a randomized study of laparoscopic Roux-en-Y gastric bypass (LYRGB) and laparoscopic adjustable gastric banding (LAGB) found LYRGB was superior to LAGB in terms of excess weight lost (76.2% vs. 46.2%), but exposed the patient to higher complication rates and more potentially lethal long-term surgical complications [19]. Restrictive procedures also promote a shorter mean time of rapid weight loss than combined procedures (9e12 vs. 12e18 months). The shape of the weight loss curve, in addition to overall amount of weight lost, is different between the two types of procedures [20,21]. Arguably the best long-term study of bariatric surgery is the Swedish obese subjects (SOS) study, a prospective, non-randomized study of 4047 obese persons, of which 2010 underwent a form of bariatric surgery. As reported by €stro € m et al. [22], the average maximum weight loss after 1e2 years was a reduction of 32% for Sjo gastric bypass, 25% for VBG, and 20% for AGB as compared to a 1e2% change in body weight resulting from traditional weight loss techniques. A 10-year follow-up found weight loss had stabilized at 25%, 16%, and 14%, respectively, for the three procedures. Complications related to bariatric surgery have been reported in subsequent pregnancies. Reported complications include internal hernias, bowel obstructions, hyperemesis, cholelithiasis and problems with position and function of the gastric band that may require revision [20,23]. A systematic review of bariatric surgery during pregnancy [24] identified 20 complications requiring surgical intervention, including multiple bowel obstructions, a gastric ulcer, a staple line stricture and several band-related complications. After RYGB, the risk of intestinal obstruction is particularly high [25]. Santulli et al. [26] observed surgery-related complications in about a one-fourth of parturients after RYGB. This is in agreement with an earlier study [27]. In light of the serious potential side effects of bariatric procedures that may arise during pregnancy, it is recommended that a high index of suspicion for gastrointestinal surgical complications be maintained when a post-operative woman presents with abdominal pain during pregnancy [28]. Wax et al. [29] further recommend that any woman with a history of RYGB should ideally have a preconception visit with an obstetrician to discuss the warning signs of small bowel obstruction and the associated risks with pregnancy post-operatively. The early involvement of a bariatric surgeon in cases of suspected bowel obstruction is also strongly encouraged [28].
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Type of procedure and pregnancy outcome Several studies have attempted to address whether a particular or subtype of bariatric procedure is superior with regard to pregnancy outcome. At the current time, the body of research is still developing as to what type of procedure or specific procedure is, if any, superior with regard to pregnancy outcome. In general, malabsorptive and restrictive procedures appear to be generally similar in terms of safety and efficacy. Gastric bypass Santulli et al. [26] studied 24 pregnancies following RYGB matched with 120 body mass index (BMI) normal and 120 BMI-matched controls for age and parity. Birthweight was lower in the post-operative cohort than both normal and BMI-matched control groups (2948.2 vs. 3368.2 and 3441.8 g, respectively, P < 0.0001). Post-operative parturients also gained less weight than normal BMI controls (5.8 vs. 13.2 kg, respectively, P < 0.0001) and were more likely to have a CD (25% vs. 9.3%, respectively, P ¼ 0.04). No difference in perinatal complications was noted. Two studies [30,31] examined women after gastric bypass and controls collected from consecutive patients that delivered around the same time matched for obesity and prior operative delivery and stratified for obesity, respectively. Wax et al. [30] found an increased risk of hypertension, but women after surgery were still more likely to be obese than controls. Otherwise, both studies found no significant differences in GDM and hypertensive disorders. Gastric banding A recent study by our group [15] compared each subject's preoperative pregnancy with two subsequent post-operative pregnancies (109 women; 327 paired pregnancies: 109 preoperative pregnancies and 218 post-operative pregnancies). The post-operative parturients had all undergone restrictive bariatric surgery (87% had laparoscopic gastric banding and 13% had silastic ring vertical gastroplasty). Surgery led to a significantly lower prepregnancy and predelivery BMI (36.7 ± 4.4 vs. 31.5 ± 5.5 kg/m2, P < 0.001; 40.6 ± 5.5 vs. 35.3 ± 6.1 kg/m2, P < 0.001, respectively). This effect was preserved in the second post-operative surgery as well (31.5 ± 5.5 vs. 31.3 ± 6.3 kg/m2, P ¼ 0.609, and 35.3 ± 6.1 vs. 35.1 ± 5.9 kg/m2, P ¼ 0.706, respectively). Rates of hypertensive disorders and GDM were significantly lower in both post-operative pregnancies. The rate of macrosomic newborns was also significantly lower in the second pregnancy after surgery. Three studies [32e34] reported similarly lowered rates of GDM, maternal weight gain and preeclampsia following surgery. A larger and more recent study of 133 parturients after LAGB concluded that post-operative pregnancies resulted in babies that were as healthy as the general population [35]. Mixed procedure studies A Danish register-based cohort study identified infants born after bariatric surgery (84.4% gastric bypass) were more likely to have a shorter mean gestation, lower mean birthweight (3312 vs. 3585 g; P < 0.001) and have a higher risk of being born small for gestational age (SGA) (adjusted odds ratio (OR) 2.29, 95% confidence interval (CI) 1.32e3.96). Infants born after surgery had a reduced risk of being large for gestational age (LGA), however (adjusted OR, 0.31; 95% CI 0.15e0.65) [12]. In one of the largest population-based matched cohort studies to date, post-operative women were more likely to have a premature (9.7% vs. 6.1%, OR 1.7, 95% CI 1.4e2.0; P < 0.001) or SGA (5.2% vs. 3.0%, OR 2.0, 95% CI1.5e2.5; P < 0.001) infant than normal or obese controls [11]. A previous study of 298 post-operative pregnancies compared to the local community rates, as it aimed to evaluate if bariatric surgery increased the risk of adverse perinatal outcome, specifically birth defects. While no significant differences were noted in adverse perinatal outcome and birth defects, the study found an increased risk of GDM (9.4% vs. 5.0%, P < 0.001), macrosomia (9.4% vs. 4.6%, P < 0.001) and CD post-operatively (25.2% vs. 12.2%, P < 0.001), but no difference in birthweight, pre-eclampsia or pregnancy complications. Importantly, post-operative women were more likely to be obese
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(BMI 30 kg/m2) than the comparison group (10.7% vs. 1.2%, P < 0.001) [6]. This difference probably explains the higher rates of GDM, macrosomia and CD as well. Comparative studies A study by our group [36] compared 394 pregnancies after a restrictive procedure with 55 pregnancies after a malabsorptive procedure. We demonstrated a higher mean birthweight following malabsorptive procedures as compared to restrictive procedures (3332.8 ± 475.5 g after RYGB compared to 3104.3 ± 578.7 g after LAGB). Other outcomes, such as Apgar scores, perinatal mortality and the prevalence of low and high birthweight neonates, were equivalent between both groups. Two smaller studies [20,37] also demonstrated comparable short-term neonatal outcomes between both procedures. However, in one study [37], infants born after RYGB had a significantly lower birthweight than after LAGB (2993 vs. 3253 g, P ¼ 0.02). Surgery-to-conception interval The American Congress of Obstetricians and Gynecologists (ACOG) currently recommends to avoid pregnancy following surgery for 12e24 months after bariatric surgery (2009, reconfirmed 2013) [28]. There is concern for potential nutritional deficiencies and adverse effects on the fetus during the period of rapid weight loss that typically lasts 6e18 months after surgery. During this period, the maternal intake is markedly reduced and the nutritional requirements of the fetus are rapidly increasing [25]. While there is a strong theoretical basis for this recommendation, the current body of research does not provide supporting evidence. Our group recently found no significant difference between 104 women who conceived during the first year after surgery and 385 that conceived after the first year. A shorter time to conception was not associated with an increased risk of pregnancy complications [38]. A similar study performed in Denmark on 286 women after RYGB, of whom 158 conceived during the first year after surgery and 128 later, found no statistically significant difference (P > 0.05) with regard to birthweight, gestational age, risk of preeclampsia, GDM, labour induction, caesarean section, postpartum haemorrhage, preterm birth, SGA, LGA, Apgar score or in the need of neonatal intensive care between women who conceived during or after the first year after surgery [39]. A recent multicenter French cohort study [37] also found neonatal outcomes were unaltered by the interval from surgery to conception. Similarly, in the largest population-based cohort study to date, no effect modification was noted by procedure type or interval from surgery to delivery was detected for preterm or SGA birth [11]. Several older studies have also demonstrated no increased risk of complications associated with fetal malnutrition, such as intrauterine growth restriction (IUGR) and malformation [27,31,33,40]. Neonatal outcomes The three most commonly reported neonatal outcomes in recent studies were prematurity, SGA and LGA/macrosomia. A selection of notable studies of neonatal outcome from the last 5 years may be seen in Table 1 [11,12,14,15,26,36e38,41]. Prematurity Obesity has been linked to an increased risk of preterm delivery. A meta-analysis [42] concluded obese and overweight women have an increased risk of having a preterm (relative risk (RR) 1.24, 95% CI 1.13e1.37) and induced preterm birth (RR 1.30, 95% CI 1.23e1.37). As preterm infants are at risk of a number of complications, lowering a mother's prepregnancy BMI with bariatric surgery has been generally regarded as reasonable. Recent research suggests postsurgical women may be at a higher risk of preterm delivery than was previously thought. In the largest study to date, Roos et al. [11] found post-operative deliveries resulted in a preterm birth in a significantly higher percentage than matched controls: 9.7% versus 6.1 (risk difference 3.6%, 95% CI 2.4e4.9%; P < 0.001). The risks were elevated for both spontaneous and
Study
Inclusion criteria Intervention
Sheiner et al., 2009 [36], Israel
Santulli et al., 2010 [26], France Lapolla et al., 2010 [41], Italy
Sheiner et al., 2011 [38], Israel Aricha-Tamir et al., 2012 [14], Israel Ducarme et al., 2013 [37], France
Amsalem et al., 2013 [15], Israel
Kjaer et al., 2013 [12], Denmark Roos et al., 2013 [11], Sweden
202 deliveries after LAGB 136 deliveries after SRVG 56 deliveries after VBG 24 pregnancies after RYGB 69 women (83 pregnancies) after LAGB
104 pregnancies < 1st postop year 144 postop pregnancies 63 neonates born after LAGB 43 neonates born <1 year postop 109 first pregnancies postop 109 second pregnancies postop 339 postop pregnancies 2511 postop births 2507 postop births
Prematurity Comparison
55 deliveries after RYGB
120 normal BMI controls 120 BMI-matched controls 120 pregnancies in obese women 858 pregnancies in normal controls 385 pregnancies > 1st postop year 144 preop pregnancies in same women 31 neonates born after RYGB 51 neonates born >1 year postop 109 preop pregnancies
1277 matched controlsa 12,379 matched controlsb 12,338 matched controlsb
SGA
LGA/Macrosomia
Cases
Controls
Cases
Controls
Cases
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
20 (9.9) 11 (8.1) 3 (5.4) NR
2 (3.6)
19 (9.4) 12 (8.8) 3 (5.4) 2 (8.3)
4 (7.3)
9 4 3 0
2 (3.6)
15 (17.6)
1 (1.4) 31 (3.6)
3 (2.9)
14 (3.6)
NR
1 (0.8) 6 (5.0) 20 (2.3)
(4.5) (2.9) (5.4) (0)
7 (8.1)
5 (4.3)
Controls
3 (2.5) 13 (10.8) 51 (6.0) 11 (9.4)
NR
12 (11.5)
32 (8.3)
NR
6 (4.2)
8 (5.6)
5 (7.9) 1 (2.5)
1 (3.2) 5 (9.8)
8 (7.1) 1 (1.1)
12 (11.1)
5 (7.9) 6 (13.9)
4 (12.6) 3 (5.9)
11 (17.5) 10 (22.5)
18 (16.7) 12 (10.8)
11 (10.1)
NR
29 (8.6) 243 (9.7)
85 (6.7) 750 (6.1)
24 (7.1)
37 (2.9)
8 (2.4)
93 (7.3)
131 (5.2)
369 (3.0)
105 (4.2)
895 (7.3)
NR ¼ Not reported. LAGB ¼ Laparoscopic adjustable gastric banding. SRVG ¼ Silastic ring vertical gastroplasty VBG ¼ vertical banded gastroplasty a Matching factors: BMI, parity, maternal age and date of delivery. b Matching factors: maternal age, parity, early pregnancy body mass index, early pregnancy smoking status, education level and year of delivery.
10 (32.3) 9 (17.6)
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Table 1 Selected studies of neonatal outcome in the last 5 years.
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medically indicated preterm delivery (5.2% vs. 3.6%; OR 1.5, 1.2e1.9; P < 0.001 and 4.5% vs. 2.5%; OR 1.8, 1.4e2.3; P < 0.001, respectively). In women with a BMI 35 kg/m2, increasing BMI made preterm delivery more likely (P ¼ 0.01). When the study group (mean BMI 32.6 kg/m2) was compared to cohorts of women with BMI 35 kg/ m2 and BMI 40 kg/m2, there was an attenuation of risk, but the risk of preterm birth remained elevated for both groups. This creates an important distinction, as the data suggest the elevated risk of preterm infants is significant only for women with an early pregnancy BMI of <35 kg/m2. Women with a more elevated BMI may have a similar risk as obese women who did not have surgery [11]. Previous studies have demonstrated a more benign picture. With the exception of Lapolla et al. [41], the majority of recent studies have indicated no increased risk of preterm delivery following restrictive or malabsorptive procedures [20,26,37,38]. Of the three older studies highlighted by systematic review [9] as particularly rigorous, two studies [30,31] found a similar risk as the general population and one study [32] found a similar risk as obese individuals to have a preterm delivery. Despite a decreased risk compared to women with an elevated BMI, women who have undergone bariatric surgery appear to constitute a unique obstetric population with an increased risk of preterm delivery. The cause of this increased risk is currently unknown, although it has been suggested that when considered with the known risk for SGA infants, this may be related to a persistent nutritional deficit. Birthweight Obese women are more likely to have macrosomic infants [43,44]. Fetal macrosomia has been linked to an increased risk of childhood and adolescent obesity [45,46]. Encouragingly, surgical weight loss in the mother promotes a lasting reduction in obesity in children born post-operatively by 52%, and a reduction in severe obesity of 45% [44]. Infants born after surgery have been repetitively shown to have a decreased mean birthweight, decreased likelihood to be macrosomic, but an increased likelihood to be born SGA. A recent systematic review of 17 studies [47] noted eight studies indicated lower birthweight and decreased risk of macrosomic infants, and five studies implicated an elevated risk of SGA infants as compared to non-obese or severely obese women. Roos et al. [11] found an increased risk for SGA infants (5.2% vs. 3.0%, OR 2.0, P < 0.001) and a decreased risk of LGA infants (4.2% vs. 7.3%, OR 0.6, P < 0.001) in a recent population based matched cohort study. A smaller study [43] also demonstrated women have an increased risk of having a SGA neonate after surgery than obese controls (17.4% vs. 5%). The risk for smaller infants may be increased following malabsorptive procedures [26,31]. A recent Denmark-wide matched cohort study found post-operative infants (84.4% after LAGB) had a lower mean birthweight (3312 vs. 3585 g; P < 0.001), lower risk of being LGA (adjusted OR 0.31, 95% CI 0.15e0.65), and higher risk of being SGA (adjusted OR 2.29, 95% CI 1.32e3.96) as compared to infants born to controls. The risk of SGA infants was greater after gastric bypass than other procedures [12]. Three previous studies [33,37,40] highlight a reduction in the number of macrosomic infants. In addition, a retrospective cohort study demonstrated post-operative women were both protected against having a macrosomic infant and more likely to have an SGA infant regardless of maternal obesity status [48]. This effect is persistent even in additional pregnancies. A reduction in macrosomic neonates into the second post-operative pregnancy (11.1% before vs. 1.1% after second pregnancy, P ¼ 0.02) was recently demonstrated by our group [15]. Taken as a whole, these studies point to a significant increase in SGA infants and potential beneficial decrease in LGA and macrosomic infants. The evidence for this outcome is strong, and women should be counselled about the potential risk before conception, if possible. We also recommend fetal weight gain be carefully monitored throughout post-operative pregnancies. Miscarriage and perinatal mortality Rare outcomes such as perinatal mortality have been difficult to assess in the studies conducted to date. The largest study to date has only been able to statistically exclude a greater than double risk of
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neonatal mortality post-operatively [11]. As demonstrated by Sheiner et al. [36], no particular type of bariatric surgery appears to increase this risk. A large, paired retrospective study (n ¼ 288), however, has recently noted a significantly higher rate of spontaneous miscarriage after bariatric surgery compared with pregnancies preceding surgery (38.9% vs. 18.8%, P < 0.001) [14]. Large, systematic studies are needed in this area. Until then, definitive conclusions cannot be made due to a relative paucity of statistically significant evidence. Nutritional deficiencies Case studies have suggested nutritional deficits may arise after bariatric surgery, particularly after malabsorptive procedures [49,50], as these procedures create a state of relative nutrient deficiency that could prevent a developing fetus from acquiring required nutrients. A nutrient deficiency could place the developing fetus at risk of congenital malformations, especially neural tube defects (NTDs). Pregnancy-associated nausea and emesis could compound this risk, by further reducing available nutrients. A recent population-based study, found post-operative parturients were more likely to be anaemic (haemoglobin <10 g/dL) than obese parturients (48% vs. 37%, OR 1.5, 95% CI 1.2e1.9, P < 0.001) [13]. It is recommended that as women with prior bariatric surgery are at an increased risk of anaemia, once common causes of anaemia have been excluded, less common causes of nutritional anaemia, such as copper deficiency, should be considered [51]. Measuring risk of congenital malformation is often used as a proxy for adverse effects of nutritional deficits. When mothers followed recommendations about diet and nutritional supplementation, a study [40] found no significant increase in risk of fetal malformations post-operatively once maternal age and preterm delivery were controlled. Recently, a Swedish study [52] showed no significant increase in congenital malformations post-operatively, but did demonstrate the risk of malformation increased with increasing maternal BMI, regardless of surgical status. This suggests lowering maternal prepregnancy BMI with bariatric surgery would lower an eventual offspring's risk of congenital malformation. Several other older studies [6,30] and a recent systematic review [47] have also not indicated an increased risk of malformation. At this time, the data are insufficient to make strong recommendations. Clinical practice is therefore guided by expert opinion. Until validated by further research, regular nutritional screening and monitoring of fetal growth is recommended. Maternal pregnancy outcomes The three most commonly reported pregnancy outcomes in recent studies were GDM, hypertensive disorders of pregnancy (preeclampsia) and CD. A selection of notable studies of pregnancy outcome from the last 5 years may be seen in Table 2 [3,12,14,15,26,36,38,41,52]. Caesarean delivery Obesity is a clear risk factor for CD and also increases the risks associated with performing an operative delivery [53,54]. Obese parturients have increased complication rates, such as longer procedures, anaesthesia complications, increased rates of excessive blood loss, wound complications, venous thromboembolism, endometritis and failure of vaginal birth after CD [55e58]. Separating a potential independent risk for operative delivery after bariatric surgery from the background risk conferred by obesity has been problematic. Generally, no strong relationship between CD and prior bariatric surgery can be demonstrated. Ducarme et al. [32] found women who had undergone LAGB had half the rate of CD as obese controls. Two studies [31,41] found a higher rate of CD when post-operative women where compared to non-obese controls, but no difference when compared to obese or severely obese controls. Several studies have identified bariatric surgery as an independent risk factor for operative delivery [6,40], but others have been unable to identify a difference [30]. Rates of CD are generally not significantly different between preoperative and post-
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Study
Inclusion Criteria Intervention
Sheiner et al., 2009 [36], Israel
Burke et al., 2010 [3], USA Santulli et al., 2010 [26], France Lapolla et al., 2010 [41], Italy Sheiner et al., 2011 [38], Israel Aricha-Tamir et al., 2012 [14], Israel Amsalem et al., 2013 [15], Israel Josefsson et al., 2013 [52], Sweden Kjaer et al., 2013 [12], Denmark
202 deliveries after LAGB 136 deliveries after SRVG 56 deliveries after VBG 354 postop pregnancies 24 pregnancies after RYGB 69 women (83 pregnancies) after LAGB 104 pregnancies < 1st postop year 144 postop pregnancies 109 109 310 339
first pregnancies postop second pregnancies postop firstborns after surgery postop pregnancies
NE/NR ¼ Not examined/Not reported. LAGB ¼ Laparoscopic adjustable gastric banding. SRVG ¼ Silastic ring vertical gastroplasty VBG ¼ vertical banded gastroplasty a Gestational hypertension alone. b Chronic and pregnancy induced diabetes. c Matching factors: BMI, parity, maternal age and date of delivery.
Comparison
55 deliveries after RYGB
346 preop pregnancies 120 normal BMI 120 BMI-matched controls 120 obese women 858 normal controls 385 pregnancies > 1st postop year 144 preop pregnancies in same women 109 preop pregnancies 2,70,805 Swedish firstborns 1277 matched controlsc
Gestational diabetes
Hypertension
Caesarean delivery
Cases
Controls
Cases
Controls
Cases
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
12 (6.0) 14 (10.0) 3 (5.5) 28 (8) 2 (8.3)
3 (5.5)
14 (6.9) 10 (7.4) 4 (7.1) NR 1 (4.2)
4 (7.3)
62 (30.7) 43 (31.6) 13 (23.2) 99 (28) 8 (33.3)
14 (25.5)
11 (10.5)
93 (27) 6 (5.0) 10 (8.3) NR 60 (50.0) 28 (7.3)
8 (5.7) 6 (5.6) 7 (6.6) 17 (5.9)b 30 (8.9)
5 (8.0)
38 (36.5)
149 (43) 19 (16) 41 (34.2) 79 (65.8) 241 (28.2) 117 (30.4)
46 (31.9)
45 (31.9)
36 (24.3)
23 (21.0)
33 (30.6) 41 (38.5) NE 111 (32.7)
30 (27.8)
16 (15.4)
1 (0.8) 3 (2.5) 28 (23.5) 21 (2.4) 43 (11.2)
28 (19.3)
24 (16.7)
21 (19.0)
8 (7.4) 5 (4.7) 26 (8.2) 10 (3.0)
3514 (1.4) 91 (7.1)
8 (9.6)a
Controls
11562 (4.7) 67 (5.2)
38 (45.9)
366 (28.7)
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Table 2 Selected studies of pregnancy outcome in the last 5 years.
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operative pregnancies. This may be related to the decrease in macrosomic neonates and increase in SGA neonates [11,31,44]. Gestational diabetes mellitus Obese women are at an increased risk of developing GDM [48]. The risk of developing GDM is intimately intertwined with maternal birthweight and preconception weight. Lageross et al. [59] were able to demonstrate the rate of GDM increased among obese women, but also among women who were born SGA or LGA. Having both risk factors conveyed an increased risk GDM. The risk of GDM due to abnormal birthweight could be reduced by normalizing maternal pregravid weight. Bariatric surgery is capable of significantly reducing the odds of developing pregestational diabetes and GDM [32,60,61]. Surgery can reduce the risk of developing GDM from the rate in similar obese parturients to a rate equivalent with the general population (8% vs. 27%) [3]. Our group recently confirmed a reduction in GDM post-operatively in a population-based study [13]. Another study was able to demonstrate that a reduction in GDM persisted in to consecutive post-operative pregnancies [15]. The interval from surgery to conception does not appear to have a significant effect on the rate of GDM, as highlighted by a study that found equivalent rates of GDM during and after the first year after surgery (10.5% vs. 7.3%, P ¼ 0.159) [38]. Hypertensive disorders of pregnancy There can be little doubt obesity increases the risk of developing hypertensive disorders of pregnancy and chronic hypertension. An elevated BMI has been shown to be a significant risk factor for developing gestational hypertension by multiple retrospective and prospective studies [4,48,62,63]. Surgery can reduce the risk of developing hypertensive disorders of pregnancy. Bennet et al. [64] were able to demonstrate a 75% reduction in hypertensive disorders. A study of 288 parturients (144 preoperative and 144 post-operative women) by our group [14] found a significant reduction in hypertensive disorders in pregnancies that followed bariatric surgery (adjusted OR 0.4, 95% CI 0.2e0.8). This trend of a reduction in hypertensive disorders also persists into additional pregnancies after surgery. A study [15] comparing one preoperative pregnancy with two pregnancies following restrictive bariatric surgery demonstrated hypertensive disorders were significantly less likely in both post-operative pregnancies (21% vs. 7.4% and 4.7%, P ¼ 0.009). These studies are in agreement with numerous other studies that have previously reported a reduction of hypertensive disorders in postoperative pregnancies [9,22,33,41,65]. In addition, a systematic review [47] noted a decreased risk of pre-eclampsia after bariatric surgery. Conclusions In conclusion, a critical review of the data to date indicates pregnancy after bariatric surgery appears to effectively reduce the risk of complications such as fetal macrosomia [11,12,15,37,48], GDM [13,15,47] and hypertensive disorders of pregnancy [14,15,40,64,65]; however, women who become pregnant after bariatric surgery may constitute a unique obstetric population with an increased risk for preterm [11] and small-for-gestational-age infants [11,12,15,37,43,48]. Comparing serial pregnancies in the same woman has allowed for important trends to be uncovered [14,15]. Significant decreases in hypertensive disorders and GDM were noted recently that, most importantly, persisted into subsequent post-operative pregnancies [15]. Recent large, population-based studies [11e13] have begun to provide the statistical power necessary to definitively describe the characteristics of this unique obstetric population. The increased risk of preterm birth brought to light by the study by Roos et al. [11] highlights the benefit of large population-based trials. Preterm birth is a relatively rare outcome, and the statistical power of this study uncovered a significant difference between post-operative women and non-obese parturients that had not been elucidated by previous studies [20,26,37]. An increase in the number of SGA infants post-operatively, while uncovered by previous studies in the last few years, has also been further validated in the last year by multiple population-based studies [11,12].
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Taken together, the increased risk of preterm and SGA neonates after surgery is concerning because it may indicate a consequence of an as yet unproven nutritional deficit in post-operative pregnancies. Conversely, it may simply suggest a trend toward more adequately grown infants that are less likely to be macrosomic. To date, studies [11,40] have not indicated an increased risk of fetal malformations, which may be a result of inadequate nutrition. A greater than double risk of malformation, however, can be safely excluded [11]. Prior maternal bariatric surgery has a profound impact on the mother and her offspring during pregnancy. Until further research has fully clarified the risks related to post-operative pregnancy, special attention to maternal nutritional deficits and fetal growth are required during pregnancy in women with a prior history of bariatric surgery. We recommend that providers treat post-operative pregnant women as a unique obstetric population. They should provide counselling and the close observation this entails.
Practice points The literature provides strong evidence that post-operative women are at a decreased risk of hypertensive disorders of pregnancy [14,15,40,64,65] and GDM [13,15,47]. Population-based trials and large comparison studies provide strong evidence that infants born in post-operative pregnancies are less likely to be born macrosomic and LGA [11,12,15,37,48], but are more likely to be premature [11] and SGA [11,12,15,37,43,48]. This effect persists in subsequent post-operative pregnancies [15]. Expert opinion recommends post-operative parturients should be monitored for nutritional deficiencies and supplementation given as required [28,51]. Expert opinion recommends close observation and regular assessment of fetal growth throughout pregnancy [28,51]. Large, retrospective studies have found no significant differences between pregnancies during and after the first year post-operatively [11,29,37,38]. Nevertheless, expert opinion still recommends avoiding pregnancy for at least the first post-operative year [28]. Post-operative women are at risk of developing surgical complications secondary to prior bariatric surgery during pregnancy. Experts strongly recommend the early involvement of a bariatric surgeon when post-operative parturients present with a potential surgical complication [28].
Research agenda Further, large population-based trials and randomized controlled trials (RTCs) should focus on characterizing the risk of fetal malformations and the potential effects of nutritional deficiencies on the developing fetus. Trials should further compare the outcomes of specific bariatric procedure types as this could potentially alter the types of procedures regularly performed on women in the future.
Conflict of interest: The authors have no conflict of interest to declare.
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[34] Dixon JB, Dixon ME, O'Brien PE. Pregnancy after Lap-Band surgery: management of the band to achieve healthy weight outcomes. Obes Surg 2001;11:59e65. [35] Carelli AM, Ren CJ, Youn HA, et al. Impact of laparoscopic adjustable gastric banding on pregnancy, maternal weight, and neonatal health. Obes Surg 2011;21:1552e8. [36] Sheiner E, Balaban E, Dreiher J, et al. Pregnancy outcome in patients following different types of bariatric surgeries. Obes Surg 2009;19:1286e92. [37] Ducarme G, Parisio L, Santulli P, et al. Neonatal outcomes in pregnancies after bariatric surgery: a retrospective multicentric cohort study in three French referral centers. J Matern Fetal Neonatal Med 2013;26:275e8. *[38] Sheiner E, Edri A, Balaban E, et al. Pregnancy outcome of patients who conceive during or after the first year following bariatric surgery. Am J Obstet Gynecol 2011;204:50.e1e6. *[39] Kjaer MM, Nilas L. Timing of pregnancy after gastric bypass-a national register-based cohort study. 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[41] Lapolla A, Marangon M, Dalfr a MG, et al. Pregnancy outcome in morbidly obese women before and after laparoscopic gastric banding. Obes Surg 2010;20:1251e7. [42] McDonald SD, Han Z, Mulla S, et al., Knowledge Synthesis Group. Overweight and obesity in mothers and risk of preterm birth and low birth weight infants: systematic review and meta-analyses. BMJ 2010;341:c3428. [43] Lesko J, Peaceman A. Pregnancy outcomes in women after bariatric surgery compared with obese and morbidly obese controls. Obstet Gynecol 2012;119:547e54. MG, Busetto L, Chilelli NC, et al. Pregnancy and foetal outcome after bariatric surgery: a review of recent studies. [44] Dalfra J Matern Fetal Neonatal Med 2012;25:1537e43. [45] Salsberry PJ, Reagan PB. Taking the long view: the prenatal environment and early adolescent overweight. Res Nurs Health 2007;30:297e307. [46] Hediger ML, Overpeck MD, McGlynn A, et al. Growth and fatness at three to six years of age of children born small- or large-for-gestational age. Pediatrics 1999;104:e33. [47] Kjaer MM, Nilas L. Pregnancy after bariatric surgeryea review of benefits and risks. Acta Obstet Gynecol Scand 2013;92: 264e71. [48] Belogolovkin V, Salihu HM, Weldeselasse H, et al. Impact of prior bariatric surgery on maternal and fetal outcomes among obese and non-obese mothers. Arch Gynecol Obstet 2012;285:1211e8. [49] Iavazzo C, Ntziora F, Rousos I, et al. Complications in pregnancy after bariatric surgery. Arch Gynecol Obstet 2010;282: 225e7. [50] Celiker MY, Chawla A. Congenital B12 deficiency following maternal gastric bypass. J Perinatol 2009;29:640e2. [51] Society for Maternal-Fetal Medicine SMFM with the assistance of Donna Johnson MD. SMFM Consult: Assessing nutritional needs in pregnant patients with prior bariatric surgery. Contemporary OB/GYN. 2013. hn A-B, et al. Risk for congenital malformations in offspring of women who have undergone [52] Josefsson A, Bladh M, Wire bariatric surgery. A national cohort. BJOG 2013;120:1477e82. [53] Gilead R, Yaniv Salem S, Sergienko R, et al. Maternal “isolated” obesity and obstetric complications. J Matern Fetal Neonatal Med 2013;25:2579e82. [54] American College of Obstetricians and Gynecologists. ACOG committee opinion no. 549: obesity in pregnancy. Obstet Gynecol 2013;121:213e7. [55] Wispelwey BP, Sheiner E. Cesarean delivery in obese women: a comprehensive review. J Matern Fetal Neonatal Med 2013;26:547e51. [56] Schneid-Kofman N, Sheiner E, Levy A, et al. Risk factors for wound infection following cesarean deliveries. Int J Gynaecol Obstet 2005;90:10e5. [57] James A. Committee on practice bulletinsdobstetrics. Practice bulletin no. 123: thromboembolism in pregnancy. Obstet Gynecol 2011;118:718e29. [58] Myles TD, Gooch J, Santolaya J. Obesity as an independent risk factor for infectious morbidity in patients who undergo cesarean delivery. Obstet Gynecol 2002;100:959e64. [59] Lagerros YT, Cnattingius S, Granath F, et al. From infancy to pregnancy: birth weight, body mass index, and the risk of gestational diabetes. Eur J Epidemiol 2012;10:799e805. [60] Smith J, Cianflone K, Biron S, et al. Effects of maternal surgical weight loss in mothers on intergenerational transmission of obesity. J Clin Endocrinol Metab 2009;94:4275e83. [61] Sheiner E, Menes TS, Silverberg D, et al. Pregnancy outcome of patients with gestational diabetes mellitus following bariatric surgery. Am J Obstet Gynecol 2006;194:431e5. [62] Ehrenthal DB, Jurkovitz C, Hoffman M, et al. Prepregnancy body mass index as an independent risk factor for pregnancyinduced hypertension. J Women's Health (Larchmt) 2011;20:67e72. [63] Dennedy MC, Avalos G, O'Reilly MW, et al. The impact of maternal obesity on gestational outcomes. Ir Med J 2012;105: 23e5. [64] Bennett WL, Gilson MM, Jamshidi R, et al. Impact of bariatric surgery on hypertensive disorders in pregnancy: retrospective analysis of insurance claims data. BMJ 2010;340. c1662. [65] Guelinckx I, Devlieger R, Donceel P, et al. Lifestyle after bariatric surgery: a multicenter, prospective cohort study in pregnant women. Obes Surg 2012;22:1456e64.
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13
Pregnancy and neonatal outcome after bariatric surgery Kent Willis, MD a, *, Nicky Lieberman, MD b, Eyal Sheiner, MD, PhD, Deputy Director General, Professor and Senior Researcher c a
Our Lady of the Lake Regional Medical Center, Baton Rouge, LA, USA Head of Community Medicine Department, Clalit Health Services Ltd., Tel Aviv, Israel c Soroka University Medical Center, Ben-Gurion University of the Negev, PO Box 151, Beer Sheva, Israel b
Keywords: bariatric surgery maternal obesity pregnancy neonatal outcome perinatal outcome pregnancy outcome
The global obesity epidemic is changing the face of maternalefetal medicine. One in five women is obese at time of conception, and increasing numbers of parturients have undergone bariatric surgery. Recent publication of large, population-based studies and comparison studies of preoperative and post-operative pregnancies have highlighted new risks and benefits to the mother and child. Pregnancy after bariatric surgery appears to effectively reduce the risk of complications such as fetal macrosomia, gestational diabetes mellitus, and hypertensive disorders of pregnancy; however, women who become pregnant after bariatric surgery may constitute a unique obstetric population with an increased risk for preterm and small-for-gestational-age infants. In this article, we provide an overview of the current knowledge of the impact of maternal bariatric surgery on neonatal and pregnancy outcomes. © 2014 Elsevier Ltd. All rights reserved.
Introduction Rising rates of obesity have created a worldwide epidemic [1]. As obesity rates in pregnant women rise, the importance of obesity-related complications also increases. Pregravid obesity has been shown
* Corresponding author. Our Lady of the Lake Children's Hospital, 5000 Hennessy Boulevard, Suite 6001, Baton Rouge, LA 70808, USA. Tel.: þ1 2254219570. E-mail addresses: [email protected] (K. Willis), [email protected] (E. Sheiner).
http://dx.doi.org/10.1016/j.bpobgyn.2014.04.015 1521-6934/© 2014 Elsevier Ltd. All rights reserved.
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to triple the risk of infertility and increase rates of miscarriage, gestational diabetes mellitus (GDM), gestational hypertension, pre-eclampsia and caesarean delivery (CD) [2e8]. Women of reproductive age are turning to bariatric surgery in increasing numbers. Currently, women aged 18-45 years undergo >50,000 inpatient bariatric surgical procedures a year in the United States [9], accounting for approximately half of all bariatric procedures [10]. This has created a new obstetric population with unique outcomes and risks for mother and child. Recent publication of large, population-based trials [11e13] and studies comparing preoperative and post-operative pregnancies [14,15] have highlighted new risks and benefits of pregnancy after surgery and confirmed prior research in this new and important field of maternalefetal and neonatal medicine. Bariatric procedures Three main classes of bariatric surgeries have been developed to date. These include restrictive, malabsorptive and combined restrictiveemalabsorptive procedures. Restrictive procedures, such as sleeve gastrectomy, vertical banded gastroplasty (VBG) and adjustable gastric banding (ABG), promote weight loss by physically decreasing gastric volume and thereby total food intake. They are generally considered safer and less complicated to perform, but they do have the disadvantage that sugary, high-energy foods may bypass the restriction. Malabsorptive procedures, such as biliopancreatic diversion (BPD), cause weight loss primarily by bypassing a significant portion of the small bowel and inducing malabsorption. Most purely malabsorptive procedures have been linked to significant safety concerns and are now rarely performed [16,17]. In the United States, most procedures are currently of the combined type, with the Roux-en-Y gastric bypass (RYGB) accounting for 93% of all procedures performed in 2000 [17]. Despite its classification, malabsorption is actually not significant in RYGB [18]. Instead, neuroendocrine changes are increasingly recognized as an important component of the weight loss effect [16]. A recent 10-year follow-up of a randomized study of laparoscopic Roux-en-Y gastric bypass (LYRGB) and laparoscopic adjustable gastric banding (LAGB) found LYRGB was superior to LAGB in terms of excess weight lost (76.2% vs. 46.2%), but exposed the patient to higher complication rates and more potentially lethal long-term surgical complications [19]. Restrictive procedures also promote a shorter mean time of rapid weight loss than combined procedures (9e12 vs. 12e18 months). The shape of the weight loss curve, in addition to overall amount of weight lost, is different between the two types of procedures [20,21]. Arguably the best long-term study of bariatric surgery is the Swedish obese subjects (SOS) study, a prospective, non-randomized study of 4047 obese persons, of which 2010 underwent a form of bariatric surgery. As reported by €stro € m et al. [22], the average maximum weight loss after 1e2 years was a reduction of 32% for Sjo gastric bypass, 25% for VBG, and 20% for AGB as compared to a 1e2% change in body weight resulting from traditional weight loss techniques. A 10-year follow-up found weight loss had stabilized at 25%, 16%, and 14%, respectively, for the three procedures. Complications related to bariatric surgery have been reported in subsequent pregnancies. Reported complications include internal hernias, bowel obstructions, hyperemesis, cholelithiasis and problems with position and function of the gastric band that may require revision [20,23]. A systematic review of bariatric surgery during pregnancy [24] identified 20 complications requiring surgical intervention, including multiple bowel obstructions, a gastric ulcer, a staple line stricture and several band-related complications. After RYGB, the risk of intestinal obstruction is particularly high [25]. Santulli et al. [26] observed surgery-related complications in about a one-fourth of parturients after RYGB. This is in agreement with an earlier study [27]. In light of the serious potential side effects of bariatric procedures that may arise during pregnancy, it is recommended that a high index of suspicion for gastrointestinal surgical complications be maintained when a post-operative woman presents with abdominal pain during pregnancy [28]. Wax et al. [29] further recommend that any woman with a history of RYGB should ideally have a preconception visit with an obstetrician to discuss the warning signs of small bowel obstruction and the associated risks with pregnancy post-operatively. The early involvement of a bariatric surgeon in cases of suspected bowel obstruction is also strongly encouraged [28].
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Type of procedure and pregnancy outcome Several studies have attempted to address whether a particular or subtype of bariatric procedure is superior with regard to pregnancy outcome. At the current time, the body of research is still developing as to what type of procedure or specific procedure is, if any, superior with regard to pregnancy outcome. In general, malabsorptive and restrictive procedures appear to be generally similar in terms of safety and efficacy. Gastric bypass Santulli et al. [26] studied 24 pregnancies following RYGB matched with 120 body mass index (BMI) normal and 120 BMI-matched controls for age and parity. Birthweight was lower in the post-operative cohort than both normal and BMI-matched control groups (2948.2 vs. 3368.2 and 3441.8 g, respectively, P < 0.0001). Post-operative parturients also gained less weight than normal BMI controls (5.8 vs. 13.2 kg, respectively, P < 0.0001) and were more likely to have a CD (25% vs. 9.3%, respectively, P ¼ 0.04). No difference in perinatal complications was noted. Two studies [30,31] examined women after gastric bypass and controls collected from consecutive patients that delivered around the same time matched for obesity and prior operative delivery and stratified for obesity, respectively. Wax et al. [30] found an increased risk of hypertension, but women after surgery were still more likely to be obese than controls. Otherwise, both studies found no significant differences in GDM and hypertensive disorders. Gastric banding A recent study by our group [15] compared each subject's preoperative pregnancy with two subsequent post-operative pregnancies (109 women; 327 paired pregnancies: 109 preoperative pregnancies and 218 post-operative pregnancies). The post-operative parturients had all undergone restrictive bariatric surgery (87% had laparoscopic gastric banding and 13% had silastic ring vertical gastroplasty). Surgery led to a significantly lower prepregnancy and predelivery BMI (36.7 ± 4.4 vs. 31.5 ± 5.5 kg/m2, P < 0.001; 40.6 ± 5.5 vs. 35.3 ± 6.1 kg/m2, P < 0.001, respectively). This effect was preserved in the second post-operative surgery as well (31.5 ± 5.5 vs. 31.3 ± 6.3 kg/m2, P ¼ 0.609, and 35.3 ± 6.1 vs. 35.1 ± 5.9 kg/m2, P ¼ 0.706, respectively). Rates of hypertensive disorders and GDM were significantly lower in both post-operative pregnancies. The rate of macrosomic newborns was also significantly lower in the second pregnancy after surgery. Three studies [32e34] reported similarly lowered rates of GDM, maternal weight gain and preeclampsia following surgery. A larger and more recent study of 133 parturients after LAGB concluded that post-operative pregnancies resulted in babies that were as healthy as the general population [35]. Mixed procedure studies A Danish register-based cohort study identified infants born after bariatric surgery (84.4% gastric bypass) were more likely to have a shorter mean gestation, lower mean birthweight (3312 vs. 3585 g; P < 0.001) and have a higher risk of being born small for gestational age (SGA) (adjusted odds ratio (OR) 2.29, 95% confidence interval (CI) 1.32e3.96). Infants born after surgery had a reduced risk of being large for gestational age (LGA), however (adjusted OR, 0.31; 95% CI 0.15e0.65) [12]. In one of the largest population-based matched cohort studies to date, post-operative women were more likely to have a premature (9.7% vs. 6.1%, OR 1.7, 95% CI 1.4e2.0; P < 0.001) or SGA (5.2% vs. 3.0%, OR 2.0, 95% CI1.5e2.5; P < 0.001) infant than normal or obese controls [11]. A previous study of 298 post-operative pregnancies compared to the local community rates, as it aimed to evaluate if bariatric surgery increased the risk of adverse perinatal outcome, specifically birth defects. While no significant differences were noted in adverse perinatal outcome and birth defects, the study found an increased risk of GDM (9.4% vs. 5.0%, P < 0.001), macrosomia (9.4% vs. 4.6%, P < 0.001) and CD post-operatively (25.2% vs. 12.2%, P < 0.001), but no difference in birthweight, pre-eclampsia or pregnancy complications. Importantly, post-operative women were more likely to be obese
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(BMI 30 kg/m2) than the comparison group (10.7% vs. 1.2%, P < 0.001) [6]. This difference probably explains the higher rates of GDM, macrosomia and CD as well. Comparative studies A study by our group [36] compared 394 pregnancies after a restrictive procedure with 55 pregnancies after a malabsorptive procedure. We demonstrated a higher mean birthweight following malabsorptive procedures as compared to restrictive procedures (3332.8 ± 475.5 g after RYGB compared to 3104.3 ± 578.7 g after LAGB). Other outcomes, such as Apgar scores, perinatal mortality and the prevalence of low and high birthweight neonates, were equivalent between both groups. Two smaller studies [20,37] also demonstrated comparable short-term neonatal outcomes between both procedures. However, in one study [37], infants born after RYGB had a significantly lower birthweight than after LAGB (2993 vs. 3253 g, P ¼ 0.02). Surgery-to-conception interval The American Congress of Obstetricians and Gynecologists (ACOG) currently recommends to avoid pregnancy following surgery for 12e24 months after bariatric surgery (2009, reconfirmed 2013) [28]. There is concern for potential nutritional deficiencies and adverse effects on the fetus during the period of rapid weight loss that typically lasts 6e18 months after surgery. During this period, the maternal intake is markedly reduced and the nutritional requirements of the fetus are rapidly increasing [25]. While there is a strong theoretical basis for this recommendation, the current body of research does not provide supporting evidence. Our group recently found no significant difference between 104 women who conceived during the first year after surgery and 385 that conceived after the first year. A shorter time to conception was not associated with an increased risk of pregnancy complications [38]. A similar study performed in Denmark on 286 women after RYGB, of whom 158 conceived during the first year after surgery and 128 later, found no statistically significant difference (P > 0.05) with regard to birthweight, gestational age, risk of preeclampsia, GDM, labour induction, caesarean section, postpartum haemorrhage, preterm birth, SGA, LGA, Apgar score or in the need of neonatal intensive care between women who conceived during or after the first year after surgery [39]. A recent multicenter French cohort study [37] also found neonatal outcomes were unaltered by the interval from surgery to conception. Similarly, in the largest population-based cohort study to date, no effect modification was noted by procedure type or interval from surgery to delivery was detected for preterm or SGA birth [11]. Several older studies have also demonstrated no increased risk of complications associated with fetal malnutrition, such as intrauterine growth restriction (IUGR) and malformation [27,31,33,40]. Neonatal outcomes The three most commonly reported neonatal outcomes in recent studies were prematurity, SGA and LGA/macrosomia. A selection of notable studies of neonatal outcome from the last 5 years may be seen in Table 1 [11,12,14,15,26,36e38,41]. Prematurity Obesity has been linked to an increased risk of preterm delivery. A meta-analysis [42] concluded obese and overweight women have an increased risk of having a preterm (relative risk (RR) 1.24, 95% CI 1.13e1.37) and induced preterm birth (RR 1.30, 95% CI 1.23e1.37). As preterm infants are at risk of a number of complications, lowering a mother's prepregnancy BMI with bariatric surgery has been generally regarded as reasonable. Recent research suggests postsurgical women may be at a higher risk of preterm delivery than was previously thought. In the largest study to date, Roos et al. [11] found post-operative deliveries resulted in a preterm birth in a significantly higher percentage than matched controls: 9.7% versus 6.1 (risk difference 3.6%, 95% CI 2.4e4.9%; P < 0.001). The risks were elevated for both spontaneous and
Study
Inclusion criteria Intervention
Sheiner et al., 2009 [36], Israel
Santulli et al., 2010 [26], France Lapolla et al., 2010 [41], Italy
Sheiner et al., 2011 [38], Israel Aricha-Tamir et al., 2012 [14], Israel Ducarme et al., 2013 [37], France
Amsalem et al., 2013 [15], Israel
Kjaer et al., 2013 [12], Denmark Roos et al., 2013 [11], Sweden
202 deliveries after LAGB 136 deliveries after SRVG 56 deliveries after VBG 24 pregnancies after RYGB 69 women (83 pregnancies) after LAGB
104 pregnancies < 1st postop year 144 postop pregnancies 63 neonates born after LAGB 43 neonates born <1 year postop 109 first pregnancies postop 109 second pregnancies postop 339 postop pregnancies 2511 postop births 2507 postop births
Prematurity Comparison
55 deliveries after RYGB
120 normal BMI controls 120 BMI-matched controls 120 pregnancies in obese women 858 pregnancies in normal controls 385 pregnancies > 1st postop year 144 preop pregnancies in same women 31 neonates born after RYGB 51 neonates born >1 year postop 109 preop pregnancies
1277 matched controlsa 12,379 matched controlsb 12,338 matched controlsb
SGA
LGA/Macrosomia
Cases
Controls
Cases
Controls
Cases
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
20 (9.9) 11 (8.1) 3 (5.4) NR
2 (3.6)
19 (9.4) 12 (8.8) 3 (5.4) 2 (8.3)
4 (7.3)
9 4 3 0
2 (3.6)
15 (17.6)
1 (1.4) 31 (3.6)
3 (2.9)
14 (3.6)
NR
1 (0.8) 6 (5.0) 20 (2.3)
(4.5) (2.9) (5.4) (0)
7 (8.1)
5 (4.3)
Controls
3 (2.5) 13 (10.8) 51 (6.0) 11 (9.4)
NR
12 (11.5)
32 (8.3)
NR
6 (4.2)
8 (5.6)
5 (7.9) 1 (2.5)
1 (3.2) 5 (9.8)
8 (7.1) 1 (1.1)
12 (11.1)
5 (7.9) 6 (13.9)
4 (12.6) 3 (5.9)
11 (17.5) 10 (22.5)
18 (16.7) 12 (10.8)
11 (10.1)
NR
29 (8.6) 243 (9.7)
85 (6.7) 750 (6.1)
24 (7.1)
37 (2.9)
8 (2.4)
93 (7.3)
131 (5.2)
369 (3.0)
105 (4.2)
895 (7.3)
NR ¼ Not reported. LAGB ¼ Laparoscopic adjustable gastric banding. SRVG ¼ Silastic ring vertical gastroplasty VBG ¼ vertical banded gastroplasty a Matching factors: BMI, parity, maternal age and date of delivery. b Matching factors: maternal age, parity, early pregnancy body mass index, early pregnancy smoking status, education level and year of delivery.
10 (32.3) 9 (17.6)
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Table 1 Selected studies of neonatal outcome in the last 5 years.
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medically indicated preterm delivery (5.2% vs. 3.6%; OR 1.5, 1.2e1.9; P < 0.001 and 4.5% vs. 2.5%; OR 1.8, 1.4e2.3; P < 0.001, respectively). In women with a BMI 35 kg/m2, increasing BMI made preterm delivery more likely (P ¼ 0.01). When the study group (mean BMI 32.6 kg/m2) was compared to cohorts of women with BMI 35 kg/ m2 and BMI 40 kg/m2, there was an attenuation of risk, but the risk of preterm birth remained elevated for both groups. This creates an important distinction, as the data suggest the elevated risk of preterm infants is significant only for women with an early pregnancy BMI of <35 kg/m2. Women with a more elevated BMI may have a similar risk as obese women who did not have surgery [11]. Previous studies have demonstrated a more benign picture. With the exception of Lapolla et al. [41], the majority of recent studies have indicated no increased risk of preterm delivery following restrictive or malabsorptive procedures [20,26,37,38]. Of the three older studies highlighted by systematic review [9] as particularly rigorous, two studies [30,31] found a similar risk as the general population and one study [32] found a similar risk as obese individuals to have a preterm delivery. Despite a decreased risk compared to women with an elevated BMI, women who have undergone bariatric surgery appear to constitute a unique obstetric population with an increased risk of preterm delivery. The cause of this increased risk is currently unknown, although it has been suggested that when considered with the known risk for SGA infants, this may be related to a persistent nutritional deficit. Birthweight Obese women are more likely to have macrosomic infants [43,44]. Fetal macrosomia has been linked to an increased risk of childhood and adolescent obesity [45,46]. Encouragingly, surgical weight loss in the mother promotes a lasting reduction in obesity in children born post-operatively by 52%, and a reduction in severe obesity of 45% [44]. Infants born after surgery have been repetitively shown to have a decreased mean birthweight, decreased likelihood to be macrosomic, but an increased likelihood to be born SGA. A recent systematic review of 17 studies [47] noted eight studies indicated lower birthweight and decreased risk of macrosomic infants, and five studies implicated an elevated risk of SGA infants as compared to non-obese or severely obese women. Roos et al. [11] found an increased risk for SGA infants (5.2% vs. 3.0%, OR 2.0, P < 0.001) and a decreased risk of LGA infants (4.2% vs. 7.3%, OR 0.6, P < 0.001) in a recent population based matched cohort study. A smaller study [43] also demonstrated women have an increased risk of having a SGA neonate after surgery than obese controls (17.4% vs. 5%). The risk for smaller infants may be increased following malabsorptive procedures [26,31]. A recent Denmark-wide matched cohort study found post-operative infants (84.4% after LAGB) had a lower mean birthweight (3312 vs. 3585 g; P < 0.001), lower risk of being LGA (adjusted OR 0.31, 95% CI 0.15e0.65), and higher risk of being SGA (adjusted OR 2.29, 95% CI 1.32e3.96) as compared to infants born to controls. The risk of SGA infants was greater after gastric bypass than other procedures [12]. Three previous studies [33,37,40] highlight a reduction in the number of macrosomic infants. In addition, a retrospective cohort study demonstrated post-operative women were both protected against having a macrosomic infant and more likely to have an SGA infant regardless of maternal obesity status [48]. This effect is persistent even in additional pregnancies. A reduction in macrosomic neonates into the second post-operative pregnancy (11.1% before vs. 1.1% after second pregnancy, P ¼ 0.02) was recently demonstrated by our group [15]. Taken as a whole, these studies point to a significant increase in SGA infants and potential beneficial decrease in LGA and macrosomic infants. The evidence for this outcome is strong, and women should be counselled about the potential risk before conception, if possible. We also recommend fetal weight gain be carefully monitored throughout post-operative pregnancies. Miscarriage and perinatal mortality Rare outcomes such as perinatal mortality have been difficult to assess in the studies conducted to date. The largest study to date has only been able to statistically exclude a greater than double risk of
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neonatal mortality post-operatively [11]. As demonstrated by Sheiner et al. [36], no particular type of bariatric surgery appears to increase this risk. A large, paired retrospective study (n ¼ 288), however, has recently noted a significantly higher rate of spontaneous miscarriage after bariatric surgery compared with pregnancies preceding surgery (38.9% vs. 18.8%, P < 0.001) [14]. Large, systematic studies are needed in this area. Until then, definitive conclusions cannot be made due to a relative paucity of statistically significant evidence. Nutritional deficiencies Case studies have suggested nutritional deficits may arise after bariatric surgery, particularly after malabsorptive procedures [49,50], as these procedures create a state of relative nutrient deficiency that could prevent a developing fetus from acquiring required nutrients. A nutrient deficiency could place the developing fetus at risk of congenital malformations, especially neural tube defects (NTDs). Pregnancy-associated nausea and emesis could compound this risk, by further reducing available nutrients. A recent population-based study, found post-operative parturients were more likely to be anaemic (haemoglobin <10 g/dL) than obese parturients (48% vs. 37%, OR 1.5, 95% CI 1.2e1.9, P < 0.001) [13]. It is recommended that as women with prior bariatric surgery are at an increased risk of anaemia, once common causes of anaemia have been excluded, less common causes of nutritional anaemia, such as copper deficiency, should be considered [51]. Measuring risk of congenital malformation is often used as a proxy for adverse effects of nutritional deficits. When mothers followed recommendations about diet and nutritional supplementation, a study [40] found no significant increase in risk of fetal malformations post-operatively once maternal age and preterm delivery were controlled. Recently, a Swedish study [52] showed no significant increase in congenital malformations post-operatively, but did demonstrate the risk of malformation increased with increasing maternal BMI, regardless of surgical status. This suggests lowering maternal prepregnancy BMI with bariatric surgery would lower an eventual offspring's risk of congenital malformation. Several other older studies [6,30] and a recent systematic review [47] have also not indicated an increased risk of malformation. At this time, the data are insufficient to make strong recommendations. Clinical practice is therefore guided by expert opinion. Until validated by further research, regular nutritional screening and monitoring of fetal growth is recommended. Maternal pregnancy outcomes The three most commonly reported pregnancy outcomes in recent studies were GDM, hypertensive disorders of pregnancy (preeclampsia) and CD. A selection of notable studies of pregnancy outcome from the last 5 years may be seen in Table 2 [3,12,14,15,26,36,38,41,52]. Caesarean delivery Obesity is a clear risk factor for CD and also increases the risks associated with performing an operative delivery [53,54]. Obese parturients have increased complication rates, such as longer procedures, anaesthesia complications, increased rates of excessive blood loss, wound complications, venous thromboembolism, endometritis and failure of vaginal birth after CD [55e58]. Separating a potential independent risk for operative delivery after bariatric surgery from the background risk conferred by obesity has been problematic. Generally, no strong relationship between CD and prior bariatric surgery can be demonstrated. Ducarme et al. [32] found women who had undergone LAGB had half the rate of CD as obese controls. Two studies [31,41] found a higher rate of CD when post-operative women where compared to non-obese controls, but no difference when compared to obese or severely obese controls. Several studies have identified bariatric surgery as an independent risk factor for operative delivery [6,40], but others have been unable to identify a difference [30]. Rates of CD are generally not significantly different between preoperative and post-
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Study
Inclusion Criteria Intervention
Sheiner et al., 2009 [36], Israel
Burke et al., 2010 [3], USA Santulli et al., 2010 [26], France Lapolla et al., 2010 [41], Italy Sheiner et al., 2011 [38], Israel Aricha-Tamir et al., 2012 [14], Israel Amsalem et al., 2013 [15], Israel Josefsson et al., 2013 [52], Sweden Kjaer et al., 2013 [12], Denmark
202 deliveries after LAGB 136 deliveries after SRVG 56 deliveries after VBG 354 postop pregnancies 24 pregnancies after RYGB 69 women (83 pregnancies) after LAGB 104 pregnancies < 1st postop year 144 postop pregnancies 109 109 310 339
first pregnancies postop second pregnancies postop firstborns after surgery postop pregnancies
NE/NR ¼ Not examined/Not reported. LAGB ¼ Laparoscopic adjustable gastric banding. SRVG ¼ Silastic ring vertical gastroplasty VBG ¼ vertical banded gastroplasty a Gestational hypertension alone. b Chronic and pregnancy induced diabetes. c Matching factors: BMI, parity, maternal age and date of delivery.
Comparison
55 deliveries after RYGB
346 preop pregnancies 120 normal BMI 120 BMI-matched controls 120 obese women 858 normal controls 385 pregnancies > 1st postop year 144 preop pregnancies in same women 109 preop pregnancies 2,70,805 Swedish firstborns 1277 matched controlsc
Gestational diabetes
Hypertension
Caesarean delivery
Cases
Controls
Cases
Controls
Cases
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
12 (6.0) 14 (10.0) 3 (5.5) 28 (8) 2 (8.3)
3 (5.5)
14 (6.9) 10 (7.4) 4 (7.1) NR 1 (4.2)
4 (7.3)
62 (30.7) 43 (31.6) 13 (23.2) 99 (28) 8 (33.3)
14 (25.5)
11 (10.5)
93 (27) 6 (5.0) 10 (8.3) NR 60 (50.0) 28 (7.3)
8 (5.7) 6 (5.6) 7 (6.6) 17 (5.9)b 30 (8.9)
5 (8.0)
38 (36.5)
149 (43) 19 (16) 41 (34.2) 79 (65.8) 241 (28.2) 117 (30.4)
46 (31.9)
45 (31.9)
36 (24.3)
23 (21.0)
33 (30.6) 41 (38.5) NE 111 (32.7)
30 (27.8)
16 (15.4)
1 (0.8) 3 (2.5) 28 (23.5) 21 (2.4) 43 (11.2)
28 (19.3)
24 (16.7)
21 (19.0)
8 (7.4) 5 (4.7) 26 (8.2) 10 (3.0)
3514 (1.4) 91 (7.1)
8 (9.6)a
Controls
11562 (4.7) 67 (5.2)
38 (45.9)
366 (28.7)
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Table 2 Selected studies of pregnancy outcome in the last 5 years.
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operative pregnancies. This may be related to the decrease in macrosomic neonates and increase in SGA neonates [11,31,44]. Gestational diabetes mellitus Obese women are at an increased risk of developing GDM [48]. The risk of developing GDM is intimately intertwined with maternal birthweight and preconception weight. Lageross et al. [59] were able to demonstrate the rate of GDM increased among obese women, but also among women who were born SGA or LGA. Having both risk factors conveyed an increased risk GDM. The risk of GDM due to abnormal birthweight could be reduced by normalizing maternal pregravid weight. Bariatric surgery is capable of significantly reducing the odds of developing pregestational diabetes and GDM [32,60,61]. Surgery can reduce the risk of developing GDM from the rate in similar obese parturients to a rate equivalent with the general population (8% vs. 27%) [3]. Our group recently confirmed a reduction in GDM post-operatively in a population-based study [13]. Another study was able to demonstrate that a reduction in GDM persisted in to consecutive post-operative pregnancies [15]. The interval from surgery to conception does not appear to have a significant effect on the rate of GDM, as highlighted by a study that found equivalent rates of GDM during and after the first year after surgery (10.5% vs. 7.3%, P ¼ 0.159) [38]. Hypertensive disorders of pregnancy There can be little doubt obesity increases the risk of developing hypertensive disorders of pregnancy and chronic hypertension. An elevated BMI has been shown to be a significant risk factor for developing gestational hypertension by multiple retrospective and prospective studies [4,48,62,63]. Surgery can reduce the risk of developing hypertensive disorders of pregnancy. Bennet et al. [64] were able to demonstrate a 75% reduction in hypertensive disorders. A study of 288 parturients (144 preoperative and 144 post-operative women) by our group [14] found a significant reduction in hypertensive disorders in pregnancies that followed bariatric surgery (adjusted OR 0.4, 95% CI 0.2e0.8). This trend of a reduction in hypertensive disorders also persists into additional pregnancies after surgery. A study [15] comparing one preoperative pregnancy with two pregnancies following restrictive bariatric surgery demonstrated hypertensive disorders were significantly less likely in both post-operative pregnancies (21% vs. 7.4% and 4.7%, P ¼ 0.009). These studies are in agreement with numerous other studies that have previously reported a reduction of hypertensive disorders in postoperative pregnancies [9,22,33,41,65]. In addition, a systematic review [47] noted a decreased risk of pre-eclampsia after bariatric surgery. Conclusions In conclusion, a critical review of the data to date indicates pregnancy after bariatric surgery appears to effectively reduce the risk of complications such as fetal macrosomia [11,12,15,37,48], GDM [13,15,47] and hypertensive disorders of pregnancy [14,15,40,64,65]; however, women who become pregnant after bariatric surgery may constitute a unique obstetric population with an increased risk for preterm [11] and small-for-gestational-age infants [11,12,15,37,43,48]. Comparing serial pregnancies in the same woman has allowed for important trends to be uncovered [14,15]. Significant decreases in hypertensive disorders and GDM were noted recently that, most importantly, persisted into subsequent post-operative pregnancies [15]. Recent large, population-based studies [11e13] have begun to provide the statistical power necessary to definitively describe the characteristics of this unique obstetric population. The increased risk of preterm birth brought to light by the study by Roos et al. [11] highlights the benefit of large population-based trials. Preterm birth is a relatively rare outcome, and the statistical power of this study uncovered a significant difference between post-operative women and non-obese parturients that had not been elucidated by previous studies [20,26,37]. An increase in the number of SGA infants post-operatively, while uncovered by previous studies in the last few years, has also been further validated in the last year by multiple population-based studies [11,12].
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Taken together, the increased risk of preterm and SGA neonates after surgery is concerning because it may indicate a consequence of an as yet unproven nutritional deficit in post-operative pregnancies. Conversely, it may simply suggest a trend toward more adequately grown infants that are less likely to be macrosomic. To date, studies [11,40] have not indicated an increased risk of fetal malformations, which may be a result of inadequate nutrition. A greater than double risk of malformation, however, can be safely excluded [11]. Prior maternal bariatric surgery has a profound impact on the mother and her offspring during pregnancy. Until further research has fully clarified the risks related to post-operative pregnancy, special attention to maternal nutritional deficits and fetal growth are required during pregnancy in women with a prior history of bariatric surgery. We recommend that providers treat post-operative pregnant women as a unique obstetric population. They should provide counselling and the close observation this entails.
Practice points The literature provides strong evidence that post-operative women are at a decreased risk of hypertensive disorders of pregnancy [14,15,40,64,65] and GDM [13,15,47]. Population-based trials and large comparison studies provide strong evidence that infants born in post-operative pregnancies are less likely to be born macrosomic and LGA [11,12,15,37,48], but are more likely to be premature [11] and SGA [11,12,15,37,43,48]. This effect persists in subsequent post-operative pregnancies [15]. Expert opinion recommends post-operative parturients should be monitored for nutritional deficiencies and supplementation given as required [28,51]. Expert opinion recommends close observation and regular assessment of fetal growth throughout pregnancy [28,51]. Large, retrospective studies have found no significant differences between pregnancies during and after the first year post-operatively [11,29,37,38]. Nevertheless, expert opinion still recommends avoiding pregnancy for at least the first post-operative year [28]. Post-operative women are at risk of developing surgical complications secondary to prior bariatric surgery during pregnancy. Experts strongly recommend the early involvement of a bariatric surgeon when post-operative parturients present with a potential surgical complication [28].
Research agenda Further, large population-based trials and randomized controlled trials (RTCs) should focus on characterizing the risk of fetal malformations and the potential effects of nutritional deficiencies on the developing fetus. Trials should further compare the outcomes of specific bariatric procedure types as this could potentially alter the types of procedures regularly performed on women in the future.
Conflict of interest: The authors have no conflict of interest to declare.
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