Elevated Placental Alkaline Phosphatase – A Soft Marker For Placental Injury

Author Information

Singhania N*, Sakpal V**, Gupta AS***.
(* First year Resident, ** Senior Resident, *** Professor. Department of Obstetrics and Gynecology, Seth GS Medical College and KEM Hospital, Mumbai, India.)


Elevated levels of serum alkaline phosphatase (ALP) is not uncommon in obstetrics. High levels of ALP may indicate HELLP syndrome, intrahepatic cholestasis, liver disease, bone disease. It is essential to remember and not to forget that it can be solely of placental origin. We present a case where alkaline phosphatase levels were highly raised and the cause was most probably placental.


Alkaline phosphatase is secreted by liver, bone, intestine and placental tissues.[1] Alkaline phosphatase is secreted by the syncitiotrophoblast layer of placenta.[2] It appears in maternal circulation between 15 to 26 weeks of gestation and increases during the third trimester.[3,4] Extremely high values of ALP has been associated with premature birth, low birth weight and intrauterine growth restriction (IUGR).[5,6]  We report a similar case, where dramatic elevation in ALP was associated with IUGR and  fetal distress in early 3rd trimester leading to preterm emergency cesarean section.

Case Report

A 26 years old gravida 2 para1 living 1 married since 7 years had registered in our hospital at 9 weeks of gestation. A routine antenatal (ANC) workup showed hemoglobin (Hb) of 13.0 gm%, serum TSH was 0.18 mIU/ml, HIV, HbsAg, and VDRL were non reactive. Her blood sugars were within normal limit. She had regular ANC follow up every 4 weekly. At 31 weeks of gestation her blood pressure (BP) was recorded as 160/100 mmHg. On per abdomen examination uterine size was 26 weeks, uterus was relaxed and fetal heart sounds (FHS) were regular. She was admitted for BP monitoring and evaluation of intrauterine growth restriction (IUGR). After admission her BP was monitored 6 hourly and was in the range of 160/100 mm Hg and hence was started on oral Nifedepine 5mg qid and oral enteric coated acetylsalicylic acid 75 mg OD. Her investigations were repeated. Urine was negative for albumin. Her Hb was 10.1 gm%, platelets were 2.0 lakh/cmm, INR was 0.86, blood urea nitrogen (BUN) was  17 mg%, creatinine was 1.4 mg%, total proteins were 6.5 gm%, albumin was 3.0 gm%, serum glutamic oxaloacetic transaminase (SGOT) was 62.0 u/l, serum glutamic pyruvic transaminase (SGPT) was 48 u/l, ALP was 1088 IU/L (normal range: 44 to 147 international units per liter (IU/L)), and uric acid was 8.2 mg%. Ultrasound  (USG) showed mean gestation age of 26 weeks and 2 days with estimated fetal weight of 836 gms and severe oligohydraminos (amniotic fluid index was 3-4 cm). Uteroplacental Doppler study revealed mean umblical artery S/D ratio of 4, pulsality index of middle cerebral artery as 1 with absent diastolic notch in both the uterine arteries. Daily fetal kick count, bi weekly non stress test (NST) and weekly Doppler were done. Two doses of injection Betnesol 12 mg, 24 hours apart were given for fetal lung maturity. Liver function test were repeated 2 days later where ALP, SGOT and SGPT values remained the same. Gamma glutamyl transferase (GGT)  was 43.3u/l. Her anti phospholipid antibody  screen was negative.  Whole abdomen ultrasound was done which showed normal findings. Gastroenterologist was consulted for highly elevated ALP. In the light of normal findings of USG and normal levels SGOT, SGPT, GGT, the gastroenterologist were of the opinion that the source of the raised ALP is extra hepatic, most probably placental. Her pregnancy was continued for another 2 weeks with close monitoring. At 32 weeks of gestation her NST showed repeated variable decelerations, hence emergency lower segment cesarean section was done. She delivered a female baby of 774 gms with Apgar score of 9/10. Placental weight was 500 gm. Neonate was admitted in NICU in view of low birth weight. Immediate postpartum serological tests showed ALP, SGOT, SGPT   levels at 1234 u/l, 44 u/l, 42 u/l respectively. Four weeks later ALP level was 256 u/l. Baby was discharged from NICU at birth weight of 1.5 kg.


Our patient had gestational hypertension and IUGR. Her platelet counts, SGOT, and  SGPT levels were normal thus excluding the diagnosis of HELLP syndrome. Her USG hepatobiliary evaluation was unremarkable. She had no renal and skeletal complaints. Thus making placenta the major source of elevated ALP, a diagnosis by exclusion. Our patient had IUGR, oligohydramnios, Doppler changes and non reactive NST; all suggestive of fetal compromise due to uteropacental insufficiency.
In one case report acutely rising ALP was attributed to placental infarction and damage that resulted in intra uterine death.[7] In another study elevated ALP was associated with spontaneous preterm birth.[8] In review of literature there is one case report of isolated elevated ALP in uncomplicated pregnancy[1] and two case reports of isolated rise in gestational diabetes mellitus (GDM).[9,10]  In one of these cases genetic abnormality was present. There is another case report of raised ALP in patient with antiphospholipid antibody syndrome.[11]  The autoimmune profile of our patient was normal and she also did not have GDM. Antenatal USG and post delivery neonatal evaluation by neonatologist did not suggest any genetic abnormality. This evidence allows us to draw an inference that the raised ALP in our patient was due to placental injury.
Thus we can postulate from the above study that extremely high placental ALP could be a biochemical marker for placental injury that can lead to adverse fetal outcomes.


In cases where adverse fetal outcome is anticipated a close watch should be kept on serial ALP levels. In patients with rising trend of ALP obstetrics Doppler study must be done to look for fetoplacental insufficiency. 

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Singhania N, Sakpal V, Gupta AS. Elevated Placental Alkaline Phosphatase – A Soft Marker For Placental Injury. JPGO 2018. Volume 5 No.3. Available from: http://www.jpgo.org/2018/03/elevated-placental-alkaline-phosphatase.html