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Vitamin K1 monitoring in pregnancies after bariatric surgery: a prospective cohort study
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Vitamin K1 MONITORING in pregnancies after bariatric surgery: a prospective cohort study Goele Jans MS, Isabelle Guelinckx PhD, Willy Voets MD, PhD, Sander Galjaard MD, Paul M.M. Van Haard PhD, Greet M. Vansant PhD, Roland Devlieger MD, PhD
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Cite this article as: Goele Jans MS, Isabelle Guelinckx PhD, Willy Voets MD, PhD, Sander Galjaard MD, Paul M.M. Van Haard PhD, Greet M. Vansant PhD, Roland Devlieger MD, PhD, Vitamin K1 MONITORING in pregnancies after bariatric surgery: a prospective cohort study, Surgery for Obesity and Related Diseases, http://dx.doi.org/ 10.1016/j.soard.2014.04.032 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
VITAMIN K1 MONITORING IN PREGNANCIES AFTER BARIATRIC SURGERY: A PROSPECTIVE COHORT STUDY
Goele Jans1 (MS), Isabelle Guelinckx2 (PhD), Willy Voets3 (MD, PhD), Sander Galjaard (MD)1-4, Paul M.M. Van Haard4 (PhD)5, Greet M. Vansant2 (PhD), Roland Devlieger1,4 (MD, PhD) 1
2
Department of Development and Regeneration, Unit Pregnancy, Fetus and Newborn, KU Leuven, Belgium Department of Public Health and Primary Care; Environment and Health, section nutrition, KU Leuven,
Belgium 3
Jessa Hospital Hasselt, Belgium
4
Department of Obstetrics and Gynecology, University Hospitals Leuven, Belgium
5
Department of Medical Laboratories/Diagnostic Centre SSDZ, Reinier de Graaf Group of Hospitals,
Association of Clinical Chemistry, Delft, the Netherlands
Funding: I. Guelinckx was funded by a post-doctoral grant from KU Leuven (2010-2011). R. Devlieger is recipient of a post-doctoral research grant from FWO Flanders (2010-2015). Corresponding author:
Roland Devlieger, MD, PhD Department of Obstetrics and Gynecology University Hospitals Leuven Herestraat 49, B-3000 Leuven, Belgium Phone: +3216344204, Fax: +3216344205 [email protected]
Acknowledgments: RD, IG, WV, SG and GV designed research. RD and IG conducted research; GJ analyzed data and wrote the paper. GJ and RD had primary responsibility for final content. All authors read and approved the final manuscript. No conflicts of interests are disclosed. Running foot:
pregnancy after bariatric surgery: vitamin K1
VITAMIN K1 MONITORING IN PREGNANCIES AFTER BARIATRIC SURGERY: A PROSPECTIVE COHORT STUDY
ABSTRACT Background: Neonatal intracranial bleedings and birth defects have been reported, possibly related to maternal vitamin K1 deficiency during pregnancy following bariatric surgery. Objective: To investigate the effects of screening and supplementation on K1 serum levels in pregnant women with bariatric surgery, and to compare K1 levels and prothrombin time (PT %) in the first trimester with pregnant women without bariatric surgery. Setting: One university and 4 peripheral hospitals Methods: A prospective cohort study including 49 pregnant women with bariatric surgery. Nutritional deficiencies were prospectively screened. In case of observed low K1 serum levels, supplementation was provided. K1 serum levels and PT (%) during the first trimester were compared with a non-surgical control group of 27 women. Results: During the first trimester, most women had low K1 serum levels (<0.8 nmol/l). Mean vitamin K1 levels were significantly lower in the surgical group compared to the nonsurgical control group (0.44 vs 0.64nmol/l; P=.016). PT (%) remained in the normal range, The surgery group showed a higher mean PT compared to the controls (111.3 vs 98.9%; P<.001) Mean K1 serum levels in the study group were higher during the third than during the first trimester (P=.014).PT (%) was significantly higher during the second and third than during the first trimester (P=.004). Most of the coagulation factors, including II, V, VII, IX and X, remained within normal ranges. Conclusion: Low circulating K1 appears to be common in pregnant women with and without bariatric surgery. Supplementation during pregnancy can restore vitamin K1 in women with bariatric surgery, potentially protecting the fetus and newborn against intracranial hemorrhage Keywords: vitamin K1, pregnancy, bariatric surgery, obesity surgery
I INTRODUCTION The global epidemic of obesity, is an important public health issue which increasingly also affects women of reproductive age (1). Because maternal obesity is a risk factor for short- and long-term maternal and fetal complications, weight loss before conception is advocated
(2)
.
Although lifestyle changes are the first-line treatment for obesity, they rarely result in successful long-term weight loss. Bariatric surgery is considered to be the most successful treatment for morbid obesity in adults
(3)
. The use of bariatric surgery has increased
exponentially over the past 10 years, particularly among women of reproductive age (4, 5). A paper by Eerdekens et al. (2010) reported five cases of neonatal intracranial bleeding, all possibly related to vitamin K deficiency following maternal bariatric surgery
(6)
. Van
Mieghem et al. (2008) presented a fatal case of fetal intracerebral bleeding due to vitamin K deficiency after prolonged maternal vomiting by a patient with slippage of a gastric band
(7)
.
Most recently, a severe case of neonatal vitamin K deficiency secondary after biliopancreatic diversion was presented by Bersani et al. (2011) (8). Kang et al. (2010) also reported 2 cases of chondrodysplasia punctate, a birth defect that is characterized by a phenotype of stippled epiphyses and that is possibly related to vitamin K deficiency (9). The monitoring of vitamin levels, is strongly advocated by experts in the field of bariatric surgery. Screening for vitamin K deficiency is usually only recommended in the malabsorptive procedures, including biliopancreatic diversion with or without duodenal switch
(10)
. Notwithstanding, there is a lack of prospective data on its
prevalence in
pregnancies after bariatric surgery. So far, only small studies that have investigated vitamin K1 serum levels in non-pregnant women
(11)
and non-surgical mothers at delivery
(12)
are
available. This last mentioned study showed that vitamin K1 levels were lower in nonsurgical pregnant women (n=10) (0.09-1.99 nmol/l) than in non-pregnant women (n=71) (0.85.3 nmol/L). More recently, Sharma et al. (2013)
(13)
compared coagulation factors between
non-pregnant lean, non-pregnant obese, pregnant lean and pregnant obese women. They reported obesity to have a stronger effect on the hypercoagulablity than pregnancy itself. The aim of this prospective study was to investigate the prevalence of low vitamin K1 serum levels in pregnant women with previous bariatric surgery, and to compare K1 serum levels and PT (%) with non-surgical pregnant subjects in the first trimester of pregnancy. Secondly, we want to investigate the effect of patient-tailored supplementation on K1 serum levels and coagulation parameters in pregnant women with bariatric surgery. II MATERIALS AND METHODS A prospective multicenter cohort study was conducted between April 2009 and January 2011 at the antenatal clinics of five hospitals in the Flemish part of Belgium. The study protocol was approved by both central and local Ethical Committees. All participants signed a written informed consent form. All pregnant women of West-European origin older than 18 with a medical history of bariatric surgery presenting at the antenatal clinic before 15 weeks gestation were eligible for recruitment in the study group. Exclusion criteria were multiple pregnancy, age under 18 and inclusion after 15 weeks gestation. Subjects were divided into two groups according to the type of bariatric procedure: a restrictive group and a malabsorptive group including the purely malabsorptive procedures as well as the mixed procedures. The control group for K1 serum levels and PT (%) consisted of pregnant women without bariatric surgery who were older than 18, presenting at the antenatal clinic before 15 weeks of gestation. During the first consultation all study participants were recommended to use a standard prenatal multivitamin supplement. In case of observed micronutrient deficiencies in the first or second trimester a patient-tailored prescription for the extra required supplement was given. In case of observed vitamin K1 deficiencies in the first or second trimester, an oral vitamin K1 supplement was prescribed at a regimen of 10mg per week. In addition to prenatal
care a dietician analyzed dietary habits and physical activity levels of participants during the first and second trimester. After the analysis, a written lifestyle advice was offered to target a gestational weight gain according to the Institute of Medicine recommendation (14). The participants’ baseline characteristics were recorded at inclusion in a study file. Follow-up assessments were based on the standard clinical protocol for pregnant women, including blood pressure measurement and urine screening for proteinuria at each antenatal visit and ultrasound measurements during the three pregnancy trimesters. Blood was collected by venipuncture after an overnight fast: at 12 weeks of gestation (first trimester), at 25 weeks of gestation (second trimester) and at birth (in a non-fasting state) (third trimester). The reference interval of the Diagnostic Centre SSDZ, at Delft, the Netherlands, for a non-pregnant adult population (0.8-5.3 nmol/L) was used to define vitamin K1 deficiencies in blood levels.
(15)
. Gestational age-specific reference intervals for
coagulation factors were adopted from the longitudinal study of Szecsi et al. 2010
(16)
,. We
used their reference intervals at 13-20 weeks, 21-28 weeks and 35-42 weeks for the screenings during the first and second pregnancy trimester and at birth respectively. Statistical analyses were performed using SPSS software (IBM SPSS Statistics Version 19). A Pvalue <.05 was considered significant. III RESULTS Fifty-four patients participated into the study. In the malabsorptive group two patients lost interest in the study and one patient had a spontaneous miscarriage. In the restrictive group one pregnancy was terminated due to severe congenital malformation in the fetus (spina bifida) and there was one multiple pregnancy. The final analysis contained 49 pregnant women (18 women with a restrictive procedure and 31 with a malabsorptive procedure). All women in the restrictive group underwent Laparoscopic Adjustable Gastric Banding (LAGB). One woman in the malabsorptive group had a Biliopancreatic Diversion (BPD), the other 30
women a Roux-en-Y Gastric Bypass (RYGB). The control group included 27 women before 16 weeks of gestation without bariatric surgery. Maternal and neonatal characteristics for the total study population and according to bariatric procedure are presented in table 1. The mean preoperative BMI was 41.51 kg/m² (range 29.157.2 kg/m²). The mean maximum weight loss after surgery was significantly higher in the malabsorptive group than in the restrictive group. Consequently, the prepregnancy weight and body mass index were also significantly lower in the malabsorptive group than in the restrictive group. The majority of women became pregnant after 12 months following bariatric surgery. Babies born in the restrictive group had a higher birth weight than those born in the malabsorptive group. Other pregnancy outcomes did not significantly differ between groups. The baseline characteristics of the control group included maternal age (29 ± 4.5 yrs), prepregnancy weight (73.67 ± 18.52 kg) and body mass index (26.44 ± 6.41 kg/m²). The mean BMI was significantly higher in the study group compared to the control group (p=0.045). (The prevalence of low vitamin K1 levels (<0.8 nmol/l) did not significantly differ between the surgical study and non-surgical control group 87.8% versus 70.4%; P=.072). The incidence of low vitamin K1 levels in the surgical study population significantly decreased from 80% (n=43/49) of the women during the first trimester to 59% (n=26/44) of the women during the second trimester and 50% (n=20/40) of the women at delivery (figure 1). In the restrictive group the incidence of low vitamin K1 levels decreased during pregnancy, although not significantly: 83% (n=15/18) of the women had a low vitamin K1 level in the first trimester, 56% (n=9/16) in the second trimester and 41% (7/17) at delivery. In the malabsorptive group the incidence of low vitamin K1 levels significantly decreased from 90% (n=28/31) during the first trimester to 61% (n=17/28) during the second trimester and 56.5% (n=13/23) at delivery..
We found a significant difference in vitamin K1 serum levels and PT (%) between the surgical and non-surgical pregnant group during the first trimester of pregnancy (table 2). K1 serum levels were significantly lower in the surgical group compared to the non-surgical control group (0.44 ± 0.48 versus 0.64 ± 0.46 nmol/l; P=.016). Although prothrombin levels remained in the normal range for both the surgical and non-surgical group, we found a higher PT (%) in the first pregnancy trimester in the surgical group compared to the non-surgical control group (111.33 ± 15.51 versus 98.85 ± 8.63%; P<.001). Patients in the surgical study group refusing to take the supplementation after diagnosis of serum vitamin K1 deficiency at baseline (1st trimester, n=40) showed low vitamin K1 levels during the second trimester (n=25/40, 63%), while the majority of participants who did take a supplement during the first trimester had a normal or high vitamin K1 status (n=3/4, 75%). During the third trimester the majority of women who did not take a vitamin K1 supplement had a low vitamin K1 level (n=18/38, 58%), while all of the women who did take a vitamin K1 supplement (n=7/7, 100%) had a normal or high vitamin K1 level. Vitamin K1 levels of the surgical study group were significantly higher during the third trimester than during the first trimester (4.70 vs 0.42 nmol/l, P=.014). No differences between the restrictive and the malabsorptive group were found. Mean PT (%) was significantly higher (P=.004) during the second trimester (119.65%) and at delivery (128%) than during the first trimester (113.18%). Table 3 shows the maternal coagulation factor levels of the surgical group throughout pregnancy. During all three trimesters the majority of participants had a normal or high PT, aPTT, factor II activity, factor VII activity, factor X activity, factor IX activity, factor V activity and factor VIII activity. IV DISCUSSION We frequently found low circulating vitamin K1 levels in pregnancies after bariatric surgery, irrespective of the type of surgery. Vitamin K1 supplementation improved vitamin K1 serum
levels effectively in those patients compliant to the proposed supplementation. Vitamin K1 serum levels during the first trimester of pregnancy were significantly lower in women with bariatric surgery compared to a control group of women without bariatric surgery.Vitamin K1, which is a co-factor for gamma-glutamyl carboxylase, is essential in the production of active coagulation factors II, VII, IX and X (14). Low circulating vitamin K1 levels can lead to a hypocoaguble state in the mother, and to possible risks for the newborn as placental transfer of supplemented vitamin K1 is far less than 10%
(17)
. In normal pregnancy, the
concentration of circulating nutrient-binding proteins decreases and the maternal metabolism is modified through hormones that redirect nutrients to the placenta and mammary gland. Pregnancy is considered to be a state of hemodilution in which blood volume and blood composition change. The red blood cell mass increases with 15-20%, which is proportionally less than the increase in blood volume by 45-50%. A decrease of biomedical indexes for minerals and trace elements parallel tothe increase in volume of red blood cells therefore takes place (18). Furthermore, the increase in fat storage in pregnancy can lead to lower levels of fat-soluble vitamins because of less bio-availability of these vitamins for metabolic activation (19). Extra caution is needed with pregnant women with a history of bariatric surgery. As vitamin K1 is a highlyfat-soluble vitamin, the presence of conjugated bile salts is needed for its absorption. Especially in the malabsorptive procedures, the reduced absorption surface, the short contact time with conjugated bile salts and missing vitamin K1 absorption loci can be responsible for lower serum vitamin K1 levels
(20)
. Thus, pregnant women with a history of
bariatric surgery have a general increased risk for hypovitaminosis. This may include low circulating vitamin K1, and at least in the case of the malabsorptive procedures, frank deficiency of vitamin K.
In our study, low circulating vitamin K1 was found to occur in both procedure groups, and K1 levels were significantly lower in the first pregnancy trimester compared to a control group of women without bariatric surgery. Most studies state that vitamin deficiencies are more common after procedures that induce malabsorption because of a decreased absorption surface, missing vitamin K1 absorption loci and a disturbed digestion due to less stomach acid (21-24)
. However, the pure restrictive procedures can also cause vitamin deficiencies due to
digestive symptoms as vomiting, food intolerance and maladaptive eating disorders
(21)
. The
case reported by Van Mieghem et al. (2008) (7) indicate that early supplementation of vitamin K1 is warranted in case of persistent food intolerance and vomiting in pregnancy. Food intolerance and vomiting occur frequently after bariatric surgery, especially after the restrictive procedures, but they are also the main symptoms of hyperemesis gravidarum. Caution in case of these symptoms is required. PT (%) levels remained in the normal range, but the surgical study group showed higher PT levels compared to the non-surgical control group. A high PT in percent equals to a shortened PT in seconds (=hypercoagulable state). Sharma and coworkers
(13)
found a stronger
correlation between a hypercoagulable state and obesity than between hypercoagulablity and pregnancy. We can possibly explain our finding by the fact that the prepregnancy BMI of our surgical study group is significantly higher than our control group. Interestingly, maternal coagulation parameters and vitamin K-dependent coagulation factors in our surgical study group remained within normal range despite low vitamin K1 serum levels, illustrating the complex and incompletely understood interaction between normal physiologic changes and surgery-induced alterations of these systems. Indeed, normal pregnancy is associated with changes in haemostasis, including an increase in the majority of clotting factors, a decrease in the quantity of natural anticoagulants and a reduction in fibrinolytic activity (25).
No standard approach for vitamin K1 deficiency screening and supplementation during pregnancy is currently available. Further research in the general pregnant population as in the specific subgroup of pregnant women with a history of bariatric surgery is needed to focus on screening and optimal way of substitution. Strength of the study is the prospective design and the addition of a non-surgical pregnant control group for the assessment of vitamin K1 serum levels and PT (%) during the first pregnancy trimester. Women’s nutritional statuses were closely followed during pregnancy at different points in gestation. We used an exhaustive biomedical assessment through blood samples. Patient-tailored prescriptions for observed deficiencies were given which mimics the real clinical substitution. A limitation is the relatively small number of participants. Therefore we were unable to draw strong conclusions, in particular on rarer neonatal and surgical complications. We did not measure des-gamma-carboxy prothrombin (DCP) in maternal blood in the current study. DCP is a highly sensitive marker for vitamin K function. As an alternative, we assessed PT, aPTT and vitamin K dependent clotting factors next to vitamin K1 levels to obtain a more adequate reflection of the vitamin K function and clotting ability. Further research should probably include DCP assessments. Furthermore seven-day food records were analyzed, but the intake of vitamin K1 in particular was not observed. As recently reported in a study of Guelinckx et al.
(26)
, diet habits in pregnant women after bariatric surgery are not optimal: only 15% had a
healthy diet. Finally, patient records are not consequent in reporting on nausea and vomiting. Therefore we could not include these conditions in our analyses, although it is well known that severe nausea and vomiting can contribute to the development of vitamin deficiencies. We can conclude that caution is required with nutritional deficiencies in pregnancies following bariatric surgery. Intensive follow-up and nutritional screening for vitamin K
deficiencies and vitamin K supplementation need to be considered. This information is relevant to all clinicians involved in the care of this growing group of patients.
References 1.
Obesity and overweight. fact sheet n.311. Last updated May 2013, accessed on June
2013. World Health Organization. . 2.
ACOG Committee Opinion number 315, September 2005. Obesity in pregnancy.
Obstet Gynecol 2005 ;106:671-5. 3.
Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg 2013
;23:427-36. 4.
Maggard MA, Yermilov I, Li Z, et al. Pregnancy and fertility following bariatric
surgery: a systematic review. JAMA 2008;300:2286-96 5.
Shekelle PG, Newberry S, Maglione M, et al. Bariatric surgery in women of
reproductive age: special concerns for pregnancy. Evid Rep Technol Assess (Full Rep) 2008 169:1-51 6.
Eerdekens A, Debeer A, Van Hoey G, et al. Maternal bariatric surgery: adverse
outcomes in neonates. Eur J Pediatr 2010;169:191-6. 7.
Van Mieghem T, Van Schoubroeck D, Depiere M, Debeer A, Hanssens M. Fetal
cerebral hemorrhage caused by vitamin K deficiency after complicated bariatric surgery. Obstet Gynecol 2008;112(2 Pt 2):434-6. 8.
Bersani I, Carolis MPD, Salvi S, Zecca E, Romagnoli C, De Carolis S. Maternal-
neonatal vitamin K deficiency secondary to maternal biliopancreatic diversion. Blood Coagul Fibrinolysis 2011;22:334-6. 9.
Kang L, Marty D, Pauli RM, Mendelsohn NJ, Prachand V, Waggoner D.
Chondrodysplasia punctata associated with malabsorption from bariatric procedures. Surg Obes Relat Dis 2010;6:99-101
10.
Pournaras DJ, le Roux CW. After bariatric surgery, what vitamins should be measured
and what supplements should be given? Clin Endocrinol 2009;71:322-5. 11.
Pietersma-de Bruyn AL, van Haard PM, Beunis MH, Hamulyak K, Kuijpers JC.
Vitamin K1 levels and coagulation factors in healthy term newborns till 4 weeks after birth. Haemostasis 1990;20:8-14 12.
Pietersma-de Bruyn AL. Thesis. Vitamin K1 in the newborn: Unversity of Leiden;
1990. 13.
Sharma S, Uprichard J, Moretti A, Boyce H, Szydlo R, Stocks G. Use of
thromboelastography to assess the combined role of pregnancy and obesity on coagulation: a prospective study. Int J Obstet Anesth 2013;22:113-8 14.
Institute of Medicine. Weight Gain During Pregnancy: Reexamining the Guidelines.
Washington DC: The National Academies Press; 2009. 15.
Van Haard PMERP-dBA. Quantitation of trans-vitamin K1 in small serum samples by
off-line mutlidimensional liquid chromatography. . Clin Chim Acta 1986;157:221-30. 16.
Szecsi PB, Jørgensen M, Klajnbard A, Andersen MR, Colov NP, Stender S.
Haemostatic reference intervals in pregnancy. Thromb Haemost 2010;103:718-27 17.
Kazzi NJ, Ilagan NB, Liang KC, Kazzi GM, Grietsell LA, Brans YW. Placental
transfer of vitamin K1 in preterm pregnancy. Obstet Gynecol 1990;75(3 Pt 1):334-7. 18.
Ladipo OA. Nutrition in pregnancy: mineral and vitamin supplements. Am J Clin Nutr
2000 ;72(1 Suppl):280S-90S 19.
Weissgerber TL, Wolfe LA. Physiological adaptation in early human pregnancy:
adaptation to balance maternal-fetal demands. Appl Physiol Nutr Metab 2006;31:1-11. 20.
de Luis DA, Pacheco D, Izaola O, Terroba MC, Cuellar L, Martin T. Clinical results
and nutritional consequences of biliopancreatic diversion: three years of follow-up. Ann Nutr Metab 2008;53:234-9
21.
Xanthakos SA. Nutritional deficiencies in obesity and after bariatric surgery. Pediatr
Clin North Am 2009;56:1105-21. 22.
Weissman A, Hagay Z, Schachter M, Dreazen E. Severe maternal and fetal electrolyte
imbalance in pregnancy after gastric surgery for morbid obesity. A case report. J Reprod Med 1995;40:813-6 23.
Ledoux S, Msika S, Moussa F, et al. Comparison of nutritional consequences of
conventional therapy of obesity, adjustable gastric banding, and gastric bypass. Obes Surg 2006;16:1041-9 24.
Donadelli SP, Junqueira-Franco MV, de Mattos Donadelli CA, et al. Daily vitamin
supplementation and hypovitaminosis after obesity surgery. Nutrition 2012;28:391-6. 25.
Thornton P, Douglas J. Coagulation in pregnancy. Best Pract Res Clin Obstet
Gynaecol 2010;24:339-52 26.
Guelinckx I, Devlieger R, Donceel P, et al. Lifestyle after bariatric surgery: A
Multicenter, prospective cohort study in pregnant women. Obes Surg 2012;22:1456-64.
Table 1. Maternal and neonatal characteristics in total study population and according to bariatric procedure Total population
Restrictive procedure
Malabsorptive
P
N=49
n=18
procedure n=31
value
Maternal age (years)
29.9 ± 4.7 (18-38)
30.4 ± 3.2 (25-36)
29.6 ± 5.4 (18-38)
.506
Preoperative weight (kg)
113.2 ± 18.0 (86-165)
108.6 ±13.5 (88-140)
115.9 ±19.9 (86-165)
.205
Preoperative BMI (kg/m²)
41.5 ± 5.9 (29-57)
40.0 ± 4.9 (31-50)
42.4 ± 6.4 (29-57)
.178
Maximum weight loss after surgery
40.7 ± 16.4 (16-80)
30.3 ± 12.6 (16-57)
46.7 ± 15.5 (22-80)
<.001
38.3 ± 27.8 (2-108)
44.9 ± 28.9 (4-108)
34.5 ± 26.9 (2-96)
.198
Prepregnancy weight (kg)
77.5 ± 15.5 (54-112)
85.7 ± 15.1 (63-110)
72.7 ± 13.7 (54-112)
.008
Prepregnancy BMI (kg/m²)
28.4 ± 5.5 (21-44)
31.6 ± 5.8 (22-44)
26.6 ± 4.3 (22-39)
.002
GWG (kg)
12.9 ± 6.8 (0-30)
13.1 ± 8.1 (0-30)
12.8 ± 6.1 (2-23)
.892
Smokers (n) (%)
12 (24.5%)
6 (33.3%)
6 (19.4%)
.316
Nulliparae (n) (%)
19 (38.8%)
6 (33.3%)
13 (41.9 %)
.551
Gestational diabetes (n) (%)
2 (6.5%)
1 (7.7%)
1 (5.6%)
1.000
PIH (n) (%)
5 (10.2%)
2 (11.1%)
3 (9.7%)
1.000
Pre-eclampsia (n) (%)
1 (2.0%)
0
1 (3.2%)
1.000
Gestational age at delivery (weeks)
38.7 ± 1.9 (29-42)
39.3 ± 1.4 (36-42)
38.3 ± 2.2 (29-41)
.094
Preterm delivery (n) (%)
5 (10.2%)
1 (5.6%)
4 (12.9%)
.639
Birth weight (kg)
3.2 ± 0.6 (0.9-4.1)
3.4 ± 0.5 (2.6-4.1)
3.1 ± 0.6 (0.9-4.1)
.024
Macrosomia (n) (%)
4 (8.2%)
3 (16.7%)
1 (3.2%)
.134
Low birth weight (n) (%) (<2.5 kg)
2 (4.1%)
0 (0%)
2 (6.5%)
.526
Birth length (cm)
49.5 ± 1.7 (46-53)
49.9 ± 1.7 (47-53)
49.1 ± 1.7 (46-53)
.092
Apgar at 1’
8.8 ± 1.1 (3-10)
9.1 ± 0.5 (8-10)
8.6 ± 1.3 (3-10)
.222
Apgar at 5’
9.5 ± 0.7 (6-10)
9.6 ± 0.5 (9-10)
9.4 ± 0.8 (6-10)
.427
NICU admission (n) (%)
4 (8.2%)
1 (5.6%)
3 (9.7%)
1.000
(kg) Interval surgery - conception (months)
Values presented as mean ± SD (range) or n (valid percentage). Differences between continuous numerical variables (mean ±SD) were analyzed with Student’s t test (variables with normal distribution) or Mann-Whitney U test (variables without normal distribution). Differences between proportions of categorical variables (n (valid percentage)) were analyzed with Pearson Chi-square test or Fisher’s Exact test (two sided P value). Significant differences have a bold P value. Abbreviations: kg (kilogram), kg/m² (kilogram per square meter), BMI (body mass index), GWG (gestational weight gain), PIH (pregnancy induced hypertension), cm (centimeter)
Table 2. Mean vitamin K1 and PT levels during the first trimester in pregnant women with a history of bariatric surgery (Study group) and pregnant non-surgical controls (Control group).
Study group
R
P-value procedure
M
Control group
P-value study - control group
Mean vitamin K1 levels (nmol/l) N=49
n=18
n=31
N=27
0.44 ± 0.48
0.64 ± 0.46 0.47 ± 0.25
0.43 ± 0.57
.016
.051
Mean PT levels (%) N=49
n=18
n=31
N=27
111.3 ± 15.51
98.85 ± 8.63 109.54 ± 10.16
112.13 ± 17.49
.622
Abbreviations: R (restrictive), M (malabsorptive), PT (prothrombin time)
<.001
Table 3. Maternal coagulation factors and vitamin K- dependent coagulation factors during pregnancy after bariatric surgery
1st trimester
2nd trimester
birth
1st trimester
2nd trimester
birth
n=42
n=39
n=29
n=42
n=40
n=31
0
1 (2.6%)
0
2 (4.8%)
2 (5.0%)
6 (19.4%)
42 (100.0%)
38 (97.4%)
26 (89.7%)
Normal
38 (90.5%)
37 (92.5%)
22 (71.0%)
High
0
0
3 (10.3%)
High
2 (4.8%)
1 (2.5%)
3 (9.7%)
Factor II (%)
n=29
n=20
n=14
Factor VII (%)
n=29
n=20
n=14
Low
0
0
0
0
1 (5.0%)
2 (14.3%)
Normal
18 (62.1%)
16 (80.0%)
7 (50.0%)
Normal
27 (93.1%)
19 (95.0%)
12 (85.7%)
High
11 (37.9%)
4 (20.0%)
7 (50.0%)
High
2 (6.9%)
0
0
Factor X (%)
n=18
n=19
n=14
Factor IX (%)
n=29
n=20
n=13
Low
0
1 (5.3%)
0
Low
1 (3.4%)
0
0
Normal
21 (75.0%)
16 (84.2%)
14 (100.0%)
28 (96.6%)
19 (95.0%)
13 (100%)
High
7 (25.0%)
2 (10.5%)
0
0
1 (5.0%)
0
Factor V (%)
n=29
n=20
n=14
n=28
n=20
n=14
Low
0
1 (5.0%)
0
Low
11 (39.3%)
4 (20.0%)
5 (38.5%)
25 (86.2%)
19 (95.0%)
13 (92.9%)
Normal
17 (60.7%)
16 (80.0%)
8 (61.5%)
4 (8.2%)
0
1 (7.1%)
0
0
0
PT (%) Low Normal
Normal High
Categorical variables are presented as n (valid percentage)
aPTT (s) Low
Low
Normal High Factor VIII (%)
High
Vitamin K1 MONITORING in pregnancies after bariatric surgery: a prospective cohort study Goele Jans MS, Isabelle Guelinckx PhD, Willy Voets MD, PhD, Sander Galjaard MD, Paul M.M. Van Haard PhD, Greet M. Vansant PhD, Roland Devlieger MD, PhD
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PII: DOI: Reference:
S1550-7289(14)00214-7 http://dx.doi.org/10.1016/j.soard.2014.04.032 SOARD2010
To appear in:
Surgery for Obesity and Related Diseases
Cite this article as: Goele Jans MS, Isabelle Guelinckx PhD, Willy Voets MD, PhD, Sander Galjaard MD, Paul M.M. Van Haard PhD, Greet M. Vansant PhD, Roland Devlieger MD, PhD, Vitamin K1 MONITORING in pregnancies after bariatric surgery: a prospective cohort study, Surgery for Obesity and Related Diseases, http://dx.doi.org/ 10.1016/j.soard.2014.04.032 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
VITAMIN K1 MONITORING IN PREGNANCIES AFTER BARIATRIC SURGERY: A PROSPECTIVE COHORT STUDY
Goele Jans1 (MS), Isabelle Guelinckx2 (PhD), Willy Voets3 (MD, PhD), Sander Galjaard (MD)1-4, Paul M.M. Van Haard4 (PhD)5, Greet M. Vansant2 (PhD), Roland Devlieger1,4 (MD, PhD) 1
2
Department of Development and Regeneration, Unit Pregnancy, Fetus and Newborn, KU Leuven, Belgium Department of Public Health and Primary Care; Environment and Health, section nutrition, KU Leuven,
Belgium 3
Jessa Hospital Hasselt, Belgium
4
Department of Obstetrics and Gynecology, University Hospitals Leuven, Belgium
5
Department of Medical Laboratories/Diagnostic Centre SSDZ, Reinier de Graaf Group of Hospitals,
Association of Clinical Chemistry, Delft, the Netherlands
Funding: I. Guelinckx was funded by a post-doctoral grant from KU Leuven (2010-2011). R. Devlieger is recipient of a post-doctoral research grant from FWO Flanders (2010-2015). Corresponding author:
Roland Devlieger, MD, PhD Department of Obstetrics and Gynecology University Hospitals Leuven Herestraat 49, B-3000 Leuven, Belgium Phone: +3216344204, Fax: +3216344205 [email protected]
Acknowledgments: RD, IG, WV, SG and GV designed research. RD and IG conducted research; GJ analyzed data and wrote the paper. GJ and RD had primary responsibility for final content. All authors read and approved the final manuscript. No conflicts of interests are disclosed. Running foot:
pregnancy after bariatric surgery: vitamin K1
VITAMIN K1 MONITORING IN PREGNANCIES AFTER BARIATRIC SURGERY: A PROSPECTIVE COHORT STUDY
ABSTRACT Background: Neonatal intracranial bleedings and birth defects have been reported, possibly related to maternal vitamin K1 deficiency during pregnancy following bariatric surgery. Objective: To investigate the effects of screening and supplementation on K1 serum levels in pregnant women with bariatric surgery, and to compare K1 levels and prothrombin time (PT %) in the first trimester with pregnant women without bariatric surgery. Setting: One university and 4 peripheral hospitals Methods: A prospective cohort study including 49 pregnant women with bariatric surgery. Nutritional deficiencies were prospectively screened. In case of observed low K1 serum levels, supplementation was provided. K1 serum levels and PT (%) during the first trimester were compared with a non-surgical control group of 27 women. Results: During the first trimester, most women had low K1 serum levels (<0.8 nmol/l). Mean vitamin K1 levels were significantly lower in the surgical group compared to the nonsurgical control group (0.44 vs 0.64nmol/l; P=.016). PT (%) remained in the normal range, The surgery group showed a higher mean PT compared to the controls (111.3 vs 98.9%; P<.001) Mean K1 serum levels in the study group were higher during the third than during the first trimester (P=.014).PT (%) was significantly higher during the second and third than during the first trimester (P=.004). Most of the coagulation factors, including II, V, VII, IX and X, remained within normal ranges. Conclusion: Low circulating K1 appears to be common in pregnant women with and without bariatric surgery. Supplementation during pregnancy can restore vitamin K1 in women with bariatric surgery, potentially protecting the fetus and newborn against intracranial hemorrhage Keywords: vitamin K1, pregnancy, bariatric surgery, obesity surgery
I INTRODUCTION The global epidemic of obesity, is an important public health issue which increasingly also affects women of reproductive age (1). Because maternal obesity is a risk factor for short- and long-term maternal and fetal complications, weight loss before conception is advocated
(2)
.
Although lifestyle changes are the first-line treatment for obesity, they rarely result in successful long-term weight loss. Bariatric surgery is considered to be the most successful treatment for morbid obesity in adults
(3)
. The use of bariatric surgery has increased
exponentially over the past 10 years, particularly among women of reproductive age (4, 5). A paper by Eerdekens et al. (2010) reported five cases of neonatal intracranial bleeding, all possibly related to vitamin K deficiency following maternal bariatric surgery
(6)
. Van
Mieghem et al. (2008) presented a fatal case of fetal intracerebral bleeding due to vitamin K deficiency after prolonged maternal vomiting by a patient with slippage of a gastric band
(7)
.
Most recently, a severe case of neonatal vitamin K deficiency secondary after biliopancreatic diversion was presented by Bersani et al. (2011) (8). Kang et al. (2010) also reported 2 cases of chondrodysplasia punctate, a birth defect that is characterized by a phenotype of stippled epiphyses and that is possibly related to vitamin K deficiency (9). The monitoring of vitamin levels, is strongly advocated by experts in the field of bariatric surgery. Screening for vitamin K deficiency is usually only recommended in the malabsorptive procedures, including biliopancreatic diversion with or without duodenal switch
(10)
. Notwithstanding, there is a lack of prospective data on its
prevalence in
pregnancies after bariatric surgery. So far, only small studies that have investigated vitamin K1 serum levels in non-pregnant women
(11)
and non-surgical mothers at delivery
(12)
are
available. This last mentioned study showed that vitamin K1 levels were lower in nonsurgical pregnant women (n=10) (0.09-1.99 nmol/l) than in non-pregnant women (n=71) (0.85.3 nmol/L). More recently, Sharma et al. (2013)
(13)
compared coagulation factors between
non-pregnant lean, non-pregnant obese, pregnant lean and pregnant obese women. They reported obesity to have a stronger effect on the hypercoagulablity than pregnancy itself. The aim of this prospective study was to investigate the prevalence of low vitamin K1 serum levels in pregnant women with previous bariatric surgery, and to compare K1 serum levels and PT (%) with non-surgical pregnant subjects in the first trimester of pregnancy. Secondly, we want to investigate the effect of patient-tailored supplementation on K1 serum levels and coagulation parameters in pregnant women with bariatric surgery. II MATERIALS AND METHODS A prospective multicenter cohort study was conducted between April 2009 and January 2011 at the antenatal clinics of five hospitals in the Flemish part of Belgium. The study protocol was approved by both central and local Ethical Committees. All participants signed a written informed consent form. All pregnant women of West-European origin older than 18 with a medical history of bariatric surgery presenting at the antenatal clinic before 15 weeks gestation were eligible for recruitment in the study group. Exclusion criteria were multiple pregnancy, age under 18 and inclusion after 15 weeks gestation. Subjects were divided into two groups according to the type of bariatric procedure: a restrictive group and a malabsorptive group including the purely malabsorptive procedures as well as the mixed procedures. The control group for K1 serum levels and PT (%) consisted of pregnant women without bariatric surgery who were older than 18, presenting at the antenatal clinic before 15 weeks of gestation. During the first consultation all study participants were recommended to use a standard prenatal multivitamin supplement. In case of observed micronutrient deficiencies in the first or second trimester a patient-tailored prescription for the extra required supplement was given. In case of observed vitamin K1 deficiencies in the first or second trimester, an oral vitamin K1 supplement was prescribed at a regimen of 10mg per week. In addition to prenatal
care a dietician analyzed dietary habits and physical activity levels of participants during the first and second trimester. After the analysis, a written lifestyle advice was offered to target a gestational weight gain according to the Institute of Medicine recommendation (14). The participants’ baseline characteristics were recorded at inclusion in a study file. Follow-up assessments were based on the standard clinical protocol for pregnant women, including blood pressure measurement and urine screening for proteinuria at each antenatal visit and ultrasound measurements during the three pregnancy trimesters. Blood was collected by venipuncture after an overnight fast: at 12 weeks of gestation (first trimester), at 25 weeks of gestation (second trimester) and at birth (in a non-fasting state) (third trimester). The reference interval of the Diagnostic Centre SSDZ, at Delft, the Netherlands, for a non-pregnant adult population (0.8-5.3 nmol/L) was used to define vitamin K1 deficiencies in blood levels.
(15)
. Gestational age-specific reference intervals for
coagulation factors were adopted from the longitudinal study of Szecsi et al. 2010
(16)
,. We
used their reference intervals at 13-20 weeks, 21-28 weeks and 35-42 weeks for the screenings during the first and second pregnancy trimester and at birth respectively. Statistical analyses were performed using SPSS software (IBM SPSS Statistics Version 19). A Pvalue <.05 was considered significant. III RESULTS Fifty-four patients participated into the study. In the malabsorptive group two patients lost interest in the study and one patient had a spontaneous miscarriage. In the restrictive group one pregnancy was terminated due to severe congenital malformation in the fetus (spina bifida) and there was one multiple pregnancy. The final analysis contained 49 pregnant women (18 women with a restrictive procedure and 31 with a malabsorptive procedure). All women in the restrictive group underwent Laparoscopic Adjustable Gastric Banding (LAGB). One woman in the malabsorptive group had a Biliopancreatic Diversion (BPD), the other 30
women a Roux-en-Y Gastric Bypass (RYGB). The control group included 27 women before 16 weeks of gestation without bariatric surgery. Maternal and neonatal characteristics for the total study population and according to bariatric procedure are presented in table 1. The mean preoperative BMI was 41.51 kg/m² (range 29.157.2 kg/m²). The mean maximum weight loss after surgery was significantly higher in the malabsorptive group than in the restrictive group. Consequently, the prepregnancy weight and body mass index were also significantly lower in the malabsorptive group than in the restrictive group. The majority of women became pregnant after 12 months following bariatric surgery. Babies born in the restrictive group had a higher birth weight than those born in the malabsorptive group. Other pregnancy outcomes did not significantly differ between groups. The baseline characteristics of the control group included maternal age (29 ± 4.5 yrs), prepregnancy weight (73.67 ± 18.52 kg) and body mass index (26.44 ± 6.41 kg/m²). The mean BMI was significantly higher in the study group compared to the control group (p=0.045). (The prevalence of low vitamin K1 levels (<0.8 nmol/l) did not significantly differ between the surgical study and non-surgical control group 87.8% versus 70.4%; P=.072). The incidence of low vitamin K1 levels in the surgical study population significantly decreased from 80% (n=43/49) of the women during the first trimester to 59% (n=26/44) of the women during the second trimester and 50% (n=20/40) of the women at delivery (figure 1). In the restrictive group the incidence of low vitamin K1 levels decreased during pregnancy, although not significantly: 83% (n=15/18) of the women had a low vitamin K1 level in the first trimester, 56% (n=9/16) in the second trimester and 41% (7/17) at delivery. In the malabsorptive group the incidence of low vitamin K1 levels significantly decreased from 90% (n=28/31) during the first trimester to 61% (n=17/28) during the second trimester and 56.5% (n=13/23) at delivery..
We found a significant difference in vitamin K1 serum levels and PT (%) between the surgical and non-surgical pregnant group during the first trimester of pregnancy (table 2). K1 serum levels were significantly lower in the surgical group compared to the non-surgical control group (0.44 ± 0.48 versus 0.64 ± 0.46 nmol/l; P=.016). Although prothrombin levels remained in the normal range for both the surgical and non-surgical group, we found a higher PT (%) in the first pregnancy trimester in the surgical group compared to the non-surgical control group (111.33 ± 15.51 versus 98.85 ± 8.63%; P<.001). Patients in the surgical study group refusing to take the supplementation after diagnosis of serum vitamin K1 deficiency at baseline (1st trimester, n=40) showed low vitamin K1 levels during the second trimester (n=25/40, 63%), while the majority of participants who did take a supplement during the first trimester had a normal or high vitamin K1 status (n=3/4, 75%). During the third trimester the majority of women who did not take a vitamin K1 supplement had a low vitamin K1 level (n=18/38, 58%), while all of the women who did take a vitamin K1 supplement (n=7/7, 100%) had a normal or high vitamin K1 level. Vitamin K1 levels of the surgical study group were significantly higher during the third trimester than during the first trimester (4.70 vs 0.42 nmol/l, P=.014). No differences between the restrictive and the malabsorptive group were found. Mean PT (%) was significantly higher (P=.004) during the second trimester (119.65%) and at delivery (128%) than during the first trimester (113.18%). Table 3 shows the maternal coagulation factor levels of the surgical group throughout pregnancy. During all three trimesters the majority of participants had a normal or high PT, aPTT, factor II activity, factor VII activity, factor X activity, factor IX activity, factor V activity and factor VIII activity. IV DISCUSSION We frequently found low circulating vitamin K1 levels in pregnancies after bariatric surgery, irrespective of the type of surgery. Vitamin K1 supplementation improved vitamin K1 serum
levels effectively in those patients compliant to the proposed supplementation. Vitamin K1 serum levels during the first trimester of pregnancy were significantly lower in women with bariatric surgery compared to a control group of women without bariatric surgery.Vitamin K1, which is a co-factor for gamma-glutamyl carboxylase, is essential in the production of active coagulation factors II, VII, IX and X (14). Low circulating vitamin K1 levels can lead to a hypocoaguble state in the mother, and to possible risks for the newborn as placental transfer of supplemented vitamin K1 is far less than 10%
(17)
. In normal pregnancy, the
concentration of circulating nutrient-binding proteins decreases and the maternal metabolism is modified through hormones that redirect nutrients to the placenta and mammary gland. Pregnancy is considered to be a state of hemodilution in which blood volume and blood composition change. The red blood cell mass increases with 15-20%, which is proportionally less than the increase in blood volume by 45-50%. A decrease of biomedical indexes for minerals and trace elements parallel tothe increase in volume of red blood cells therefore takes place (18). Furthermore, the increase in fat storage in pregnancy can lead to lower levels of fat-soluble vitamins because of less bio-availability of these vitamins for metabolic activation (19). Extra caution is needed with pregnant women with a history of bariatric surgery. As vitamin K1 is a highlyfat-soluble vitamin, the presence of conjugated bile salts is needed for its absorption. Especially in the malabsorptive procedures, the reduced absorption surface, the short contact time with conjugated bile salts and missing vitamin K1 absorption loci can be responsible for lower serum vitamin K1 levels
(20)
. Thus, pregnant women with a history of
bariatric surgery have a general increased risk for hypovitaminosis. This may include low circulating vitamin K1, and at least in the case of the malabsorptive procedures, frank deficiency of vitamin K.
In our study, low circulating vitamin K1 was found to occur in both procedure groups, and K1 levels were significantly lower in the first pregnancy trimester compared to a control group of women without bariatric surgery. Most studies state that vitamin deficiencies are more common after procedures that induce malabsorption because of a decreased absorption surface, missing vitamin K1 absorption loci and a disturbed digestion due to less stomach acid (21-24)
. However, the pure restrictive procedures can also cause vitamin deficiencies due to
digestive symptoms as vomiting, food intolerance and maladaptive eating disorders
(21)
. The
case reported by Van Mieghem et al. (2008) (7) indicate that early supplementation of vitamin K1 is warranted in case of persistent food intolerance and vomiting in pregnancy. Food intolerance and vomiting occur frequently after bariatric surgery, especially after the restrictive procedures, but they are also the main symptoms of hyperemesis gravidarum. Caution in case of these symptoms is required. PT (%) levels remained in the normal range, but the surgical study group showed higher PT levels compared to the non-surgical control group. A high PT in percent equals to a shortened PT in seconds (=hypercoagulable state). Sharma and coworkers
(13)
found a stronger
correlation between a hypercoagulable state and obesity than between hypercoagulablity and pregnancy. We can possibly explain our finding by the fact that the prepregnancy BMI of our surgical study group is significantly higher than our control group. Interestingly, maternal coagulation parameters and vitamin K-dependent coagulation factors in our surgical study group remained within normal range despite low vitamin K1 serum levels, illustrating the complex and incompletely understood interaction between normal physiologic changes and surgery-induced alterations of these systems. Indeed, normal pregnancy is associated with changes in haemostasis, including an increase in the majority of clotting factors, a decrease in the quantity of natural anticoagulants and a reduction in fibrinolytic activity (25).
No standard approach for vitamin K1 deficiency screening and supplementation during pregnancy is currently available. Further research in the general pregnant population as in the specific subgroup of pregnant women with a history of bariatric surgery is needed to focus on screening and optimal way of substitution. Strength of the study is the prospective design and the addition of a non-surgical pregnant control group for the assessment of vitamin K1 serum levels and PT (%) during the first pregnancy trimester. Women’s nutritional statuses were closely followed during pregnancy at different points in gestation. We used an exhaustive biomedical assessment through blood samples. Patient-tailored prescriptions for observed deficiencies were given which mimics the real clinical substitution. A limitation is the relatively small number of participants. Therefore we were unable to draw strong conclusions, in particular on rarer neonatal and surgical complications. We did not measure des-gamma-carboxy prothrombin (DCP) in maternal blood in the current study. DCP is a highly sensitive marker for vitamin K function. As an alternative, we assessed PT, aPTT and vitamin K dependent clotting factors next to vitamin K1 levels to obtain a more adequate reflection of the vitamin K function and clotting ability. Further research should probably include DCP assessments. Furthermore seven-day food records were analyzed, but the intake of vitamin K1 in particular was not observed. As recently reported in a study of Guelinckx et al.
(26)
, diet habits in pregnant women after bariatric surgery are not optimal: only 15% had a
healthy diet. Finally, patient records are not consequent in reporting on nausea and vomiting. Therefore we could not include these conditions in our analyses, although it is well known that severe nausea and vomiting can contribute to the development of vitamin deficiencies. We can conclude that caution is required with nutritional deficiencies in pregnancies following bariatric surgery. Intensive follow-up and nutritional screening for vitamin K
deficiencies and vitamin K supplementation need to be considered. This information is relevant to all clinicians involved in the care of this growing group of patients.
References 1.
Obesity and overweight. fact sheet n.311. Last updated May 2013, accessed on June
2013. World Health Organization. . 2.
ACOG Committee Opinion number 315, September 2005. Obesity in pregnancy.
Obstet Gynecol 2005 ;106:671-5. 3.
Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg 2013
;23:427-36. 4.
Maggard MA, Yermilov I, Li Z, et al. Pregnancy and fertility following bariatric
surgery: a systematic review. JAMA 2008;300:2286-96 5.
Shekelle PG, Newberry S, Maglione M, et al. Bariatric surgery in women of
reproductive age: special concerns for pregnancy. Evid Rep Technol Assess (Full Rep) 2008 169:1-51 6.
Eerdekens A, Debeer A, Van Hoey G, et al. Maternal bariatric surgery: adverse
outcomes in neonates. Eur J Pediatr 2010;169:191-6. 7.
Van Mieghem T, Van Schoubroeck D, Depiere M, Debeer A, Hanssens M. Fetal
cerebral hemorrhage caused by vitamin K deficiency after complicated bariatric surgery. Obstet Gynecol 2008;112(2 Pt 2):434-6. 8.
Bersani I, Carolis MPD, Salvi S, Zecca E, Romagnoli C, De Carolis S. Maternal-
neonatal vitamin K deficiency secondary to maternal biliopancreatic diversion. Blood Coagul Fibrinolysis 2011;22:334-6. 9.
Kang L, Marty D, Pauli RM, Mendelsohn NJ, Prachand V, Waggoner D.
Chondrodysplasia punctata associated with malabsorption from bariatric procedures. Surg Obes Relat Dis 2010;6:99-101
10.
Pournaras DJ, le Roux CW. After bariatric surgery, what vitamins should be measured
and what supplements should be given? Clin Endocrinol 2009;71:322-5. 11.
Pietersma-de Bruyn AL, van Haard PM, Beunis MH, Hamulyak K, Kuijpers JC.
Vitamin K1 levels and coagulation factors in healthy term newborns till 4 weeks after birth. Haemostasis 1990;20:8-14 12.
Pietersma-de Bruyn AL. Thesis. Vitamin K1 in the newborn: Unversity of Leiden;
1990. 13.
Sharma S, Uprichard J, Moretti A, Boyce H, Szydlo R, Stocks G. Use of
thromboelastography to assess the combined role of pregnancy and obesity on coagulation: a prospective study. Int J Obstet Anesth 2013;22:113-8 14.
Institute of Medicine. Weight Gain During Pregnancy: Reexamining the Guidelines.
Washington DC: The National Academies Press; 2009. 15.
Van Haard PMERP-dBA. Quantitation of trans-vitamin K1 in small serum samples by
off-line mutlidimensional liquid chromatography. . Clin Chim Acta 1986;157:221-30. 16.
Szecsi PB, Jørgensen M, Klajnbard A, Andersen MR, Colov NP, Stender S.
Haemostatic reference intervals in pregnancy. Thromb Haemost 2010;103:718-27 17.
Kazzi NJ, Ilagan NB, Liang KC, Kazzi GM, Grietsell LA, Brans YW. Placental
transfer of vitamin K1 in preterm pregnancy. Obstet Gynecol 1990;75(3 Pt 1):334-7. 18.
Ladipo OA. Nutrition in pregnancy: mineral and vitamin supplements. Am J Clin Nutr
2000 ;72(1 Suppl):280S-90S 19.
Weissgerber TL, Wolfe LA. Physiological adaptation in early human pregnancy:
adaptation to balance maternal-fetal demands. Appl Physiol Nutr Metab 2006;31:1-11. 20.
de Luis DA, Pacheco D, Izaola O, Terroba MC, Cuellar L, Martin T. Clinical results
and nutritional consequences of biliopancreatic diversion: three years of follow-up. Ann Nutr Metab 2008;53:234-9
21.
Xanthakos SA. Nutritional deficiencies in obesity and after bariatric surgery. Pediatr
Clin North Am 2009;56:1105-21. 22.
Weissman A, Hagay Z, Schachter M, Dreazen E. Severe maternal and fetal electrolyte
imbalance in pregnancy after gastric surgery for morbid obesity. A case report. J Reprod Med 1995;40:813-6 23.
Ledoux S, Msika S, Moussa F, et al. Comparison of nutritional consequences of
conventional therapy of obesity, adjustable gastric banding, and gastric bypass. Obes Surg 2006;16:1041-9 24.
Donadelli SP, Junqueira-Franco MV, de Mattos Donadelli CA, et al. Daily vitamin
supplementation and hypovitaminosis after obesity surgery. Nutrition 2012;28:391-6. 25.
Thornton P, Douglas J. Coagulation in pregnancy. Best Pract Res Clin Obstet
Gynaecol 2010;24:339-52 26.
Guelinckx I, Devlieger R, Donceel P, et al. Lifestyle after bariatric surgery: A
Multicenter, prospective cohort study in pregnant women. Obes Surg 2012;22:1456-64.
Table 1. Maternal and neonatal characteristics in total study population and according to bariatric procedure Total population
Restrictive procedure
Malabsorptive
P
N=49
n=18
procedure n=31
value
Maternal age (years)
29.9 ± 4.7 (18-38)
30.4 ± 3.2 (25-36)
29.6 ± 5.4 (18-38)
.506
Preoperative weight (kg)
113.2 ± 18.0 (86-165)
108.6 ±13.5 (88-140)
115.9 ±19.9 (86-165)
.205
Preoperative BMI (kg/m²)
41.5 ± 5.9 (29-57)
40.0 ± 4.9 (31-50)
42.4 ± 6.4 (29-57)
.178
Maximum weight loss after surgery
40.7 ± 16.4 (16-80)
30.3 ± 12.6 (16-57)
46.7 ± 15.5 (22-80)
<.001
38.3 ± 27.8 (2-108)
44.9 ± 28.9 (4-108)
34.5 ± 26.9 (2-96)
.198
Prepregnancy weight (kg)
77.5 ± 15.5 (54-112)
85.7 ± 15.1 (63-110)
72.7 ± 13.7 (54-112)
.008
Prepregnancy BMI (kg/m²)
28.4 ± 5.5 (21-44)
31.6 ± 5.8 (22-44)
26.6 ± 4.3 (22-39)
.002
GWG (kg)
12.9 ± 6.8 (0-30)
13.1 ± 8.1 (0-30)
12.8 ± 6.1 (2-23)
.892
Smokers (n) (%)
12 (24.5%)
6 (33.3%)
6 (19.4%)
.316
Nulliparae (n) (%)
19 (38.8%)
6 (33.3%)
13 (41.9 %)
.551
Gestational diabetes (n) (%)
2 (6.5%)
1 (7.7%)
1 (5.6%)
1.000
PIH (n) (%)
5 (10.2%)
2 (11.1%)
3 (9.7%)
1.000
Pre-eclampsia (n) (%)
1 (2.0%)
0
1 (3.2%)
1.000
Gestational age at delivery (weeks)
38.7 ± 1.9 (29-42)
39.3 ± 1.4 (36-42)
38.3 ± 2.2 (29-41)
.094
Preterm delivery (n) (%)
5 (10.2%)
1 (5.6%)
4 (12.9%)
.639
Birth weight (kg)
3.2 ± 0.6 (0.9-4.1)
3.4 ± 0.5 (2.6-4.1)
3.1 ± 0.6 (0.9-4.1)
.024
Macrosomia (n) (%)
4 (8.2%)
3 (16.7%)
1 (3.2%)
.134
Low birth weight (n) (%) (<2.5 kg)
2 (4.1%)
0 (0%)
2 (6.5%)
.526
Birth length (cm)
49.5 ± 1.7 (46-53)
49.9 ± 1.7 (47-53)
49.1 ± 1.7 (46-53)
.092
Apgar at 1’
8.8 ± 1.1 (3-10)
9.1 ± 0.5 (8-10)
8.6 ± 1.3 (3-10)
.222
Apgar at 5’
9.5 ± 0.7 (6-10)
9.6 ± 0.5 (9-10)
9.4 ± 0.8 (6-10)
.427
NICU admission (n) (%)
4 (8.2%)
1 (5.6%)
3 (9.7%)
1.000
(kg) Interval surgery - conception (months)
Values presented as mean ± SD (range) or n (valid percentage). Differences between continuous numerical variables (mean ±SD) were analyzed with Student’s t test (variables with normal distribution) or Mann-Whitney U test (variables without normal distribution). Differences between proportions of categorical variables (n (valid percentage)) were analyzed with Pearson Chi-square test or Fisher’s Exact test (two sided P value). Significant differences have a bold P value. Abbreviations: kg (kilogram), kg/m² (kilogram per square meter), BMI (body mass index), GWG (gestational weight gain), PIH (pregnancy induced hypertension), cm (centimeter)
Table 2. Mean vitamin K1 and PT levels during the first trimester in pregnant women with a history of bariatric surgery (Study group) and pregnant non-surgical controls (Control group).
Study group
R
P-value procedure
M
Control group
P-value study - control group
Mean vitamin K1 levels (nmol/l) N=49
n=18
n=31
N=27
0.44 ± 0.48
0.64 ± 0.46 0.47 ± 0.25
0.43 ± 0.57
.016
.051
Mean PT levels (%) N=49
n=18
n=31
N=27
111.3 ± 15.51
98.85 ± 8.63 109.54 ± 10.16
112.13 ± 17.49
.622
Abbreviations: R (restrictive), M (malabsorptive), PT (prothrombin time)
<.001
Table 3. Maternal coagulation factors and vitamin K- dependent coagulation factors during pregnancy after bariatric surgery
1st trimester
2nd trimester
birth
1st trimester
2nd trimester
birth
n=42
n=39
n=29
n=42
n=40
n=31
0
1 (2.6%)
0
2 (4.8%)
2 (5.0%)
6 (19.4%)
42 (100.0%)
38 (97.4%)
26 (89.7%)
Normal
38 (90.5%)
37 (92.5%)
22 (71.0%)
High
0
0
3 (10.3%)
High
2 (4.8%)
1 (2.5%)
3 (9.7%)
Factor II (%)
n=29
n=20
n=14
Factor VII (%)
n=29
n=20
n=14
Low
0
0
0
0
1 (5.0%)
2 (14.3%)
Normal
18 (62.1%)
16 (80.0%)
7 (50.0%)
Normal
27 (93.1%)
19 (95.0%)
12 (85.7%)
High
11 (37.9%)
4 (20.0%)
7 (50.0%)
High
2 (6.9%)
0
0
Factor X (%)
n=18
n=19
n=14
Factor IX (%)
n=29
n=20
n=13
Low
0
1 (5.3%)
0
Low
1 (3.4%)
0
0
Normal
21 (75.0%)
16 (84.2%)
14 (100.0%)
28 (96.6%)
19 (95.0%)
13 (100%)
High
7 (25.0%)
2 (10.5%)
0
0
1 (5.0%)
0
Factor V (%)
n=29
n=20
n=14
n=28
n=20
n=14
Low
0
1 (5.0%)
0
Low
11 (39.3%)
4 (20.0%)
5 (38.5%)
25 (86.2%)
19 (95.0%)
13 (92.9%)
Normal
17 (60.7%)
16 (80.0%)
8 (61.5%)
4 (8.2%)
0
1 (7.1%)
0
0
0
PT (%) Low Normal
Normal High
Categorical variables are presented as n (valid percentage)
aPTT (s) Low
Low
Normal High Factor VIII (%)
High